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Sample records for single prognostic biomarker

  1. Prognostic biomarkers in osteoarthritis

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    Attur, Mukundan; Krasnokutsky-Samuels, Svetlana; Samuels, Jonathan; Abramson, Steven B.

    2013-01-01

    Purpose of review Identification of patients at risk for incident disease or disease progression in osteoarthritis remains challenging, as radiography is an insensitive reflection of molecular changes that presage cartilage and bone abnormalities. Thus there is a widely appreciated need for biochemical and imaging biomarkers. We describe recent developments with such biomarkers to identify osteoarthritis patients who are at risk for disease progression. Recent findings The biochemical markers currently under evaluation include anabolic, catabolic, and inflammatory molecules representing diverse biological pathways. A few promising cartilage and bone degradation and synthesis biomarkers are in various stages of development, awaiting further validation in larger populations. A number of studies have shown elevated expression levels of inflammatory biomarkers, both locally (synovial fluid) and systemically (serum and plasma). These chemical biomarkers are under evaluation in combination with imaging biomarkers to predict early onset and the burden of disease. Summary Prognostic biomarkers may be used in clinical knee osteoarthritis to identify subgroups in whom the disease progresses at different rates. This could facilitate our understanding of the pathogenesis and allow us to differentiate phenotypes within a heterogeneous knee osteoarthritis population. Ultimately, such findings may help facilitate the development of disease-modifying osteoarthritis drugs (DMOADs). PMID:23169101

  2. Diagnostic and prognostic epigenetic biomarkers in cancer.

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    Costa-Pinheiro, Pedro; Montezuma, Diana; Henrique, Rui; Jerónimo, Carmen

    2015-01-01

    Growing cancer incidence and mortality worldwide demands development of accurate biomarkers to perfect detection, diagnosis, prognostication and monitoring. Urologic (prostate, bladder, kidney), lung, breast and colorectal cancers are the most common and despite major advances in their characterization, this has seldom translated into biomarkers amenable for clinical practice. Epigenetic alterations are innovative cancer biomarkers owing to stability, frequency, reversibility and accessibility in body fluids, entailing great potential of assay development to assist in patient management. Several studies identified putative epigenetic cancer biomarkers, some of which have been commercialized. However, large multicenter validation studies are required to foster translation to the clinics. Herein we review the most promising epigenetic detection, diagnostic, prognostic and predictive biomarkers for the most common cancers.

  3. Glycosylation-Based Serum Biomarkers for Cancer Diagnostics and Prognostics.

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    Kirwan, Alan; Utratna, Marta; O'Dwyer, Michael E; Joshi, Lokesh; Kilcoyne, Michelle

    2015-01-01

    Cancer is the second most common cause of death in developed countries with approximately 14 million newly diagnosed individuals and over 6 million cancer-related deaths in 2012. Many cancers are discovered at a more advanced stage but better survival rates are correlated with earlier detection. Current clinically approved cancer biomarkers are most effective when applied to patients with widespread cancer. Single biomarkers with satisfactory sensitivity and specificity have not been identified for the most common cancers and some biomarkers are ineffective for the detection of early stage cancers. Thus, novel biomarkers with better diagnostic and prognostic performance are required. Aberrant protein glycosylation is well known hallmark of cancer and represents a promising source of potential biomarkers. Glycoproteins enter circulation from tissues or blood cells through active secretion or leakage and patient serum is an attractive option as a source for biomarkers from a clinical and diagnostic perspective. A plethora of technical approaches have been developed to address the challenges of glycosylation structure detection and determination. This review summarises currently utilised glycoprotein biomarkers and novel glycosylation-based biomarkers from the serum glycoproteome under investigation as cancer diagnostics and for monitoring and prognostics and includes details of recent high throughput and other emerging glycoanalytical techniques.

  4. Evaluating biomarkers for prognostic enrichment of clinical trials.

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    Kerr, Kathleen F; Roth, Jeremy; Zhu, Kehao; Thiessen-Philbrook, Heather; Meisner, Allison; Wilson, Francis Perry; Coca, Steven; Parikh, Chirag R

    2017-12-01

    A potential use of biomarkers is to assist in prognostic enrichment of clinical trials, where only patients at relatively higher risk for an outcome of interest are eligible for the trial. We investigated methods for evaluating biomarkers for prognostic enrichment. We identified five key considerations when considering a biomarker and a screening threshold for prognostic enrichment: (1) clinical trial sample size, (2) calendar time to enroll the trial, (3) total patient screening costs and the total per-patient trial costs, (4) generalizability of trial results, and (5) ethical evaluation of trial eligibility criteria. Items (1)-(3) are amenable to quantitative analysis. We developed the Biomarker Prognostic Enrichment Tool for evaluating biomarkers for prognostic enrichment at varying levels of screening stringency. We demonstrate that both modestly prognostic and strongly prognostic biomarkers can improve trial metrics using Biomarker Prognostic Enrichment Tool. Biomarker Prognostic Enrichment Tool is available as a webtool at http://prognosticenrichment.com and as a package for the R statistical computing platform. In some clinical settings, even biomarkers with modest prognostic performance can be useful for prognostic enrichment. In addition to the quantitative analysis provided by Biomarker Prognostic Enrichment Tool, investigators must consider the generalizability of trial results and evaluate the ethics of trial eligibility criteria.

  5. Distinguishing prognostic and predictive biomarkers: An information theoretic approach.

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    Sechidis, Konstantinos; Papangelou, Konstantinos; Metcalfe, Paul D; Svensson, David; Weatherall, James; Brown, Gavin

    2018-05-02

    The identification of biomarkers to support decision-making is central to personalised medicine, in both clinical and research scenarios. The challenge can be seen in two halves: identifying predictive markers, which guide the development/use of tailored therapies; and identifying prognostic markers, which guide other aspects of care and clinical trial planning, i.e. prognostic markers can be considered as covariates for stratification. Mistakenly assuming a biomarker to be predictive, when it is in fact largely prognostic (and vice-versa) is highly undesirable, and can result in financial, ethical and personal consequences. We present a framework for data-driven ranking of biomarkers on their prognostic/predictive strength, using a novel information theoretic method. This approach provides a natural algebra to discuss and quantify the individual predictive and prognostic strength, in a self-consistent mathematical framework. Our contribution is a novel procedure, INFO+, which naturally distinguishes the prognostic vs predictive role of each biomarker and handles higher order interactions. In a comprehensive empirical evaluation INFO+ outperforms more complex methods, most notably when noise factors dominate, and biomarkers are likely to be falsely identified as predictive, when in fact they are just strongly prognostic. Furthermore, we show that our methods can be 1-3 orders of magnitude faster than competitors, making it useful for biomarker discovery in 'big data' scenarios. Finally, we apply our methods to identify predictive biomarkers on two real clinical trials, and introduce a new graphical representation that provides greater insight into the prognostic and predictive strength of each biomarker. R implementations of the suggested methods are available at https://github.com/sechidis. konstantinos.sechidis@manchester.ac.uk. Supplementary data are available at Bioinformatics online.

  6. Serum prognostic biomarkers in head and neck cancer patients.

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    Lin, Ho-Sheng; Siddiq, Fauzia; Talwar, Harvinder S; Chen, Wei; Voichita, Calin; Draghici, Sorin; Jeyapalan, Gerald; Chatterjee, Madhumita; Fribley, Andrew; Yoo, George H; Sethi, Seema; Kim, Harold; Sukari, Ammar; Folbe, Adam J; Tainsky, Michael A

    2014-08-01

    A reliable estimate of survival is important as it may impact treatment choice. The objective of this study is to identify serum autoantibody biomarkers that can be used to improve prognostication for patients affected with head and neck squamous cell carcinoma (HNSCC). Prospective cohort study. A panel of 130 serum biomarkers, previously selected for cancer detection using microarray-based serological profiling and specialized bioinformatics, were evaluated for their potential as prognostic biomarkers in a cohort of 119 HNSCC patients followed for up to 12.7 years. A biomarker was considered positive if its reactivity to the particular patient's serum was greater than one standard deviation above the mean reactivity to sera from the other 118 patients, using a leave-one-out cross-validation model. Survival curves were estimated according to the Kaplan-Meier method, and statistically significant differences in survival were examined using the log rank test. Independent prognostic biomarkers were identified following analysis using multivariate Cox proportional hazards models. Poor overall survival was associated with African Americans (hazard ratio [HR] for death = 2.61; 95% confidence interval [CI]: 1.58-4.33; P = .000), advanced stage (HR = 2.79; 95% CI: 1.40-5.57; P = .004), and recurrent disease (HR = 6.66; 95% CI: 2.54-17.44; P = .000). On multivariable Cox analysis adjusted for covariates (race and stage), six of the 130 markers evaluated were found to be independent prognosticators of overall survival. The results shown here are promising and demonstrate the potential use of serum biomarkers for prognostication in HNSCC patients. Further clinical trials to include larger samples of patients across multiple centers may be warranted. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  7. Prognostic and predictive biomarkers in colorectal cancer. Towards precision medicine

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    Reimers, Marlies Suzanne

    2015-01-01

    The aim of this thesis was to define prognostic and predictive biomarkers in colorectal cancer for improved risk stratification and treatment benefit in the individual patient, with the introduction of precision medicine in the near future as the ultimate goal. By definition, precision medicine is

  8. Evaluating the quality of research into a single prognostic biomarker: a systematic review and meta-analysis of 83 studies of C-reactive protein in stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Harry Hemingway

    2010-06-01

    Full Text Available Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP with fatal and nonfatal events among patients with stable coronary disease.We searched MEDLINE (1966 to 2009 and EMBASE (1980 to 2009 and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17 from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78-2.17, with substantial heterogeneity (I(2 = 79.5. Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol and these had a relative risk of 1.65 (95% CI 1.39-1.96, I(2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001 using a validated method reduced the relative risk to 1.19 (95% CI 1.13-1.25. Only two studies reported a measure of discrimination (c-statistic. In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57-0.66.Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis

  9. MicroRNA dysregulation as a prognostic biomarker in colorectal cancer

    International Nuclear Information System (INIS)

    Dong, Yujuan; Yu, Jun; Ng, Simon SM

    2014-01-01

    Colorectal cancer (CRC) is one of the most potentially curable cancers, yet it remains the fourth most common overall cause of cancer death worldwide. The identification of robust molecular prognostic biomarkers can refine the conventional tumor–node–metastasis staging system, avoid understaging of tumor, and help pinpoint patients with early-stage CRC who may benefit from aggressive treatments. Recently, epigenetic studies have provided new molecular evidence to better categorize the CRC subtypes and predict clinical outcomes. In this review, we summarize recent findings concerning the prognostic potential of microRNAs (miRNAs) in CRC. We first discuss the prognostic value of three tissue miRNAs (miR-21-5p, miR-29-3p, miR-148-3p) that have been examined in multiple studies. We also summarize the dysregulation of miRNA processing machinery DICER in CRC and its association with risk for mortality. We also reviewe the potential application of miRNA-associated single-nucleotide polymorphisms as prognostic biomarkers for CRC, especially the miRNA-associated polymorphism in the KRAS gene. Last but not least, we discuss the microsatellite instability-related miRNA candidates. Among all these candidates, miR-21-5p is the most promising prognostic marker, yet further prospective validation studies are required before it can go into clinical usage

  10. Biomarker assessment and molecular testing for prognostication in breast cancer.

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    Kos, Zuzana; Dabbs, David J

    2016-01-01

    Current treatment of breast cancer incorporates clinical, pathological and molecular data. Oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) define prognosis and identify tumours for targeted therapy, and remain the sole established single-molecule biomarkers defining the minimum breast cancer pathology data set. Ki67 remains one of the most promising yet controversial biomarkers in breast cancer, implemented routinely in some, but not all, pathology departments. Beyond the single-molecule biomarkers, a host of multigene expression tests have been developed to interrogate the driver pathways and biology of individual breast cancers to predict clinical outcome more accurately. A minority of these assays have entered into clinical practice. This review focuses on the established biomarkers of ER, PR and HER2, the controversial but clinically implemented biomarker Ki67 and the currently marketed gene expression signatures. © 2015 John Wiley & Sons Ltd.

  11. Prognostic and predictive potential molecular biomarkers in colon cancer.

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    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  12. Racial Differences in and Prognostic Value of Biomarkers of Hyperglycemia.

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    Parrinello, Christina M; Sharrett, A Richey; Maruthur, Nisa M; Bergenstal, Richard M; Grams, Morgan E; Coresh, Josef; Selvin, Elizabeth

    2016-04-01

    We compared levels and associations of traditional (fasting glucose, HbA1c) and nontraditional (fructosamine, glycated albumin, and 1,5-anhydroglucitol [1,5-AG]) biomarkers of hyperglycemia with incident cardiovascular disease (CVD), incident end-stage renal disease (ESRD), and prevalent retinopathy in black and white adults. We included 10,373 participants without (8,096 white, 2,277 black) and 727 with diagnosed diabetes (425 white, 302 black) from the Atherosclerosis Risk in Communities (ARIC) Study. We used Cox proportional hazards models to compare hazards ratios of CVD and ESRD among blacks and whites from baseline (1990-1992) through 2012. We compared the odds ratios (from logistic regression) of retinopathy among blacks and whites. We tested for the interaction of each biomarker with race. Median values of biomarkers were higher among blacks versus whites (all P 0.10). The prognostic value of HbA1c, fructosamine, glycated albumin, and 1,5-AG with incident CVD, incident ESRD, and prevalent retinopathy were similar by race. Our results support similar interpretation of HbA1c and nontraditional biomarkers of hyperglycemia among black and whites with respect to long-term complications. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Accelerating tuberculosis vaccine trials with diagnostic and prognostic biomarkers.

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    Kaufmann, Stefan H E; Weiner, January; Maertzdorf, Jeroen

    2017-08-01

    The most recent estimates on tuberculosis (TB) morbidity and mortality reveal that the global disease burden is even higher than previously assumed. Better drugs, diagnostics and vaccines are major requirements to control the ongoing TB pandemic. The high complexity of the infectious process and the underlying pathology, however, challenge elucidation of protective immune mechanisms at the various stages towards active TB disease, which need to be understood for rational design of novel intervention measures. Areas covered: Next to the more classical approaches, host biomarkers increasingly receive attention as promising tools on our way to control the disease. In the area of diagnosis, host biomarkers are recognized as promising new means because the identification of small biosignatures with high discriminatory and even prognostic potential has stimulated the hope that rapid and easy-to-perform diagnosis and prognosis will become possible in the near future. For rational design of new vaccine candidates, correlates of protection are highly desirable. High-throughput systems-vaccinology will boost the identification of such biomarker profiles. Expert commentary: Considering their potential to accelerate development of better diagnostics and vaccines, host biomarkers should be firmly integrated into future TB research.

  14. The Prognostic Value of Serum Biomarkers in Localized Bone Sarcoma

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Maretty-Kongstad, Katja; Keller, Johnny

    2016-01-01

    sarcoma were included. Of these patients, 63 were diagnosed with chondrosarcoma and 109 patients with Ewing/osteosarcoma. The median age was 55 years for chondrosarcoma and 19 years for Ewing/osteosarcoma patients. The overall 5-year mortality was 31% [95% confidence interval (CI): 21-44] and 41% (95% CI......OBJECTIVE: Certain biomarkers such as the C-reactive protein, serum albumin, and the neutrophils to lymphocyte ratio are of prognostic significance regarding survival in different types of cancers. Data from sarcoma patients are sparse and mainly derived from soft tissue sarcoma and/or metastatic...... with localized bone sarcomas and to adjust for potential confounders. MATERIAL AND METHODS: All patients diagnosed with localized intermediate and high-grade bone sarcoma during 1994 to 2008 were extracted from the Aarhus Sarcoma Registry. The serum levels of albumin, C-reactive protein, hemoglobin, neutrophils...

  15. Osteopontin is a prognostic biomarker in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Rud, Ane Kongsgaard; Mælandsmo, Gunhild M; Boye, Kjetil; Øijordsbakken, Miriam; Lund-Iversen, Marius; Halvorsen, Ann Rita; Solberg, Steinar K; Berge, Gisle; Helland, Åslaug; Brustugun, Odd Terje

    2013-01-01

    In a previously published report we characterized the expression of the metastasis-associated proteins S100A4, osteopontin (OPN) and ephrin-A1 in a prospectively collected panel of non-small cell lung cancer (NSCLC) tumors. The aim of the present follow-up study was to investigate the prognostic impact of these potential biomarkers in the same patient cohort. In addition, circulating serum levels of OPN were measured and single nucleotide polymorphisms (SNP) in the -443 position of the OPN promoter were analyzed. Associations between immunohistochemical expression of S100A4, OPN and ephrin-A1 and relapse free and overall survival were examined using univariate and multivariate analyses. Serum OPN was measured by ELISA, polymorphisms in the -443 position of the tumor OPN promoter were analyzed by PCR, and associations between OPN levels and promoter polymorphisms and clinicopathological parameters and patient outcome were investigated. High expression of OPN in NSCLC tumors was associated with poor patient outcome, and OPN was a strong, independent prognostic factor for both relapse free and overall survival. Serum OPN levels increased according to tumor pT classification and tumor size, and patients with OPN-expressing tumors had higher serum levels than patients with OPN-negative tumors. S100A4 was a negative prognostic factor in several subgroups of adenocarcinoma patients, but not in the overall patient cohort. There was no association between ephrin-A1 expression and patient outcome. OPN is a promising prognostic biomarker in NSCLC, and should be further explored in the selection of patients for adjuvant treatment following surgical resection

  16. Matrix Metalloproteinases Polymorphisms as Prognostic Biomarkers in Malignant Pleural Mesothelioma

    Directory of Open Access Journals (Sweden)

    Danijela Štrbac

    2017-01-01

    Full Text Available Background. Malignant pleural mesothelioma (MPM is a rare disease with a relatively short overall survival (OS. Metalloproteinases (MMPs have a vast biological effect on tumor progression, invasion, metastasis formation, and apoptosis. MMP expression was previously associated with survival in MPM. Our aim was to evaluate if genetic variability of MMP genes could also serve as a prognostic biomarker in MPM. Methods. We genotyped 199 MPM patients for ten polymorphisms: rs243865, rs243849 and rs7201, in MMP2; rs17576, rs17577, rs20544, and rs2250889 in MMP9; and rs1042703, rs1042704, and rs743257 in MMP14. We determined the influence on survival using Cox regression. Results. Carriers of polymorphic MMP9 rs2250889 allele had shorter time to progression (TTP (6.07 versus 10.03 months, HR = 2.45, 95% CI = 1.45–4.14, p=0.001 and OS (9.23 versus 19.2 months, HR = 2.39, 95% CI = 1.37–4.18, p=0.002. In contrast, carriers of at least one polymorphic MMP9 rs20544 allele had longer TTP (10.93 versus 9.40 months, HR = 0.57, 95% CI = 0.38–0.86 p=0.007 and OS (20.67 versus 13.50 months, HR = 0.56, 95% CI = 0.37–0.85, p=0.007. MMP14 rs1042703 was associated with nominally shorter TTP (8.7 versus 9.27 months, HR = 2.09, 95% CI = 1.06–4.12, p=0.032. Conclusions. Selected MMP SNPs were associated with survival and could be used as potential genetic biomarkers in MPM.

  17. Prognostic Biomarkers Used for Localised Prostate Cancer Management: A Systematic Review.

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    Lamy, Pierre-Jean; Allory, Yves; Gauchez, Anne-Sophie; Asselain, Bernard; Beuzeboc, Philippe; de Cremoux, Patricia; Fontugne, Jacqueline; Georges, Agnès; Hennequin, Christophe; Lehmann-Che, Jacqueline; Massard, Christophe; Millet, Ingrid; Murez, Thibaut; Schlageter, Marie-Hélène; Rouvière, Olivier; Kassab-Chahmi, Diana; Rozet, François; Descotes, Jean-Luc; Rébillard, Xavier

    2017-03-07

    Prostate cancer stratification is based on tumour size, pretreatment PSA level, and Gleason score, but it remains imperfect. Current research focuses on the discovery and validation of novel prognostic biomarkers to improve the identification of patients at risk of aggressive cancer or of tumour relapse. This systematic review by the Intergroupe Coopérateur Francophone de Recherche en Onco-urologie (ICFuro) analysed new evidence on the analytical validity and clinical validity and utility of six prognostic biomarkers (PHI, 4Kscore, MiPS, GPS, Prolaris, Decipher). All available data for the six biomarkers published between January 2002 and April 2015 were systematically searched and reviewed. The main endpoints were aggressive prostate cancer prediction, additional value compared to classical prognostic parameters, and clinical benefit for patients with localised prostate cancer. The preanalytical and analytical validations were heterogeneous for all tests and often not adequate for the molecular signatures. Each biomarker was studied for specific indications (candidates for a first or second biopsy, and potential candidates for active surveillance, radical prostatectomy, or adjuvant treatment) for which the level of evidence (LOE) was variable. PHI and 4Kscore were the biomarkers with the highest LOE for discriminating aggressive and indolent tumours in different indications. Blood biomarkers (PHI and 4Kscore) have the highest LOE for the prediction of more aggressive prostate cancer and could help clinicians to manage patients with localised prostate cancer. The other biomarkers show a potential prognostic value; however, they should be evaluated in additional studies to confirm their clinical validity. We reviewed studies assessing the value of six prognostic biomarkers for prostate cancer. On the basis of the available evidence, some biomarkers could help in discriminating between aggressive and non-aggressive tumours with an additional value compared to the

  18. A simulation study on estimating biomarker-treatment interaction effects in randomized trials with prognostic variables.

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    Haller, Bernhard; Ulm, Kurt

    2018-02-20

    To individualize treatment decisions based on patient characteristics, identification of an interaction between a biomarker and treatment is necessary. Often such potential interactions are analysed using data from randomized clinical trials intended for comparison of two treatments. Tests of interactions are often lacking statistical power and we investigated if and how a consideration of further prognostic variables can improve power and decrease the bias of estimated biomarker-treatment interactions in randomized clinical trials with time-to-event outcomes. A simulation study was performed to assess how prognostic factors affect the estimate of the biomarker-treatment interaction for a time-to-event outcome, when different approaches, like ignoring other prognostic factors, including all available covariates or using variable selection strategies, are applied. Different scenarios regarding the proportion of censored observations, the correlation structure between the covariate of interest and further potential prognostic variables, and the strength of the interaction were considered. The simulation study revealed that in a regression model for estimating a biomarker-treatment interaction, the probability of detecting a biomarker-treatment interaction can be increased by including prognostic variables that are associated with the outcome, and that the interaction estimate is biased when relevant prognostic variables are not considered. However, the probability of a false-positive finding increases if too many potential predictors are included or if variable selection is performed inadequately. We recommend undertaking an adequate literature search before data analysis to derive information about potential prognostic variables and to gain power for detecting true interaction effects and pre-specifying analyses to avoid selective reporting and increased false-positive rates.

  19. New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia

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    Moorman, Anthony V.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is a heterogeneous disease at the genetic level. Chromosomal abnormalities are used as diagnostic, prognostic and predictive biomarkers to provide subtype, outcome and drug response information. t(12;21)/ETV6-RUNX1 and high hyper-diploidy are good-risk prognostic biomarkers whereas KMT2A (MLL) translocations, t(17;19)/TCF3-HLF, haploidy or low hypodiploidy are high-risk biomarkers. t(9;22)/BCR-ABL1 patients require targeted treatment (imatinib/dasatinib), whereas iAMP21 patients achieve better outcomes when treated intensively. High-risk genetic biomarkers are four times more prevalent in adults compared to children. The application of genomic technologies to cases without an established abnormality (B-other) reveals copy number alterations which can be used either individually or in combination as prognostic biomarkers. Transcriptome sequencing studies have identified a network of fusion genes involving kinase genes - ABL1, ABL2, PDGFRB, CSF1R, CRLF2, JAK2 and EPOR. In vitro and in vivo studies along with emerging clinical observations indicate that patients with a kinase-activating aberration may respond to treatment with small molecular inhibitors like imatinib/dasatinib and ruxolitinib. Further work is required to determine the true frequency of these abnormalities across the age spectrum and the optimal way to incorporate such inhibitors into protocols. In conclusion, genetic biomarkers are playing an increasingly important role in the management of patients with ALL. PMID:27033238

  20. Exosomal proteins as prognostic biomarkers in non-small cell lung cancer

    DEFF Research Database (Denmark)

    Sandfeld-Paulsen, B; Aggerholm-Pedersen, N; Bæk, R

    2016-01-01

    BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection...... Bonferroni correction. Results were adjusted for clinico-pathological characteristics, stage, histology, age, sex and performance status. CONCLUSION: We illustrate the promising aspects associated with the use of exosomal membrane-bound proteins as a biomarker and demonstrate that they are a strong...

  1. Identification of prognostic and diagnostic biomarkers of glucose intolerance in ApoE3Leiden mice

    NARCIS (Netherlands)

    Wopereis, S.; Radonjic, M.; Rubingh, C.; Erk, M. van; Smilde, A.; Duyvenvoorde, W. van; Cnubben, N.; Kooistra, T.; Ommen, B. van; Kleemann, R.

    2012-01-01

    The prevalence of diabetes mellitus Type 2 could be significantly reduced by early identification of subjects at risk, allowing for better prevention and earlier treatment. Glucose intolerance (GI) is a hallmark of the prediabetic stage. This study aims at identifying 1) prognostic biomarkers

  2. Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

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    Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

    2012-01-01

    Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

  3. Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.

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    Wang, Thomas J; Wollert, Kai C; Larson, Martin G; Coglianese, Erin; McCabe, Elizabeth L; Cheng, Susan; Ho, Jennifer E; Fradley, Michael G; Ghorbani, Anahita; Xanthakis, Vanessa; Kempf, Tibor; Benjamin, Emelia J; Levy, Daniel; Vasan, Ramachandran S; Januzzi, James L

    2012-09-25

    Biomarkers for predicting cardiovascular events in community-based populations have not consistently added information to standard risk factors. A limitation of many previously studied biomarkers is their lack of cardiovascular specificity. To determine the prognostic value of 3 novel biomarkers induced by cardiovascular stress, we measured soluble ST2, growth differentiation factor-15, and high-sensitivity troponin I in 3428 participants (mean age, 59 years; 53% women) in the Framingham Heart Study. We performed multivariable-adjusted proportional hazards models to assess the individual and combined ability of the biomarkers to predict adverse outcomes. We also constructed a "multimarker" score composed of the 3 biomarkers in addition to B-type natriuretic peptide and high-sensitivity C-reactive protein. During a mean follow-up of 11.3 years, there were 488 deaths, 336 major cardiovascular events, 162 heart failure events, and 142 coronary events. In multivariable-adjusted models, the 3 new biomarkers were associated with each end point (Pstatistic (P=0.005 or lower) and net reclassification improvement (P=0.001 or lower). Multiple biomarkers of cardiovascular stress are detectable in ambulatory individuals and add prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.

  4. Measuring and combining multiple diagnostic and prognostic sepsis biomarkers

    DEFF Research Database (Denmark)

    Kofoed, K.

    This PhD-thesis is based on work performed at Clinical Research Centre and Department of Infectious Diseases at Copenhagen University Hospital, Hvidovre, and includes a review, a method development study, and two clinical studies. The background of the thesis is, that timely and accurate diagnosis...... of sepsis is of great importance for choice of treatment, level of monitoring and prognosis. In this biomarkers could be a significant aid, and thus the search for and application of "new" sepsis biomarkers is of great importance. The thesis reviews the definitions and the epidemiology, and gives...

  5. Proteome screening of pleural effusions identifies galectin 1 as a diagnostic biomarker and highlights several prognostic biomarkers for malignant mesothelioma.

    Science.gov (United States)

    Mundt, Filip; Johansson, Henrik J; Forshed, Jenny; Arslan, Sertaç; Metintas, Muzaffer; Dobra, Katalin; Lehtiö, Janne; Hjerpe, Anders

    2014-03-01

    Malignant mesothelioma is an aggressive asbestos-induced cancer, and affected patients have a median survival of approximately one year after diagnosis. It is often difficult to reach a conclusive diagnosis, and ancillary measurements of soluble biomarkers could increase diagnostic accuracy. Unfortunately, few soluble mesothelioma biomarkers are suitable for clinical application. Here we screened the effusion proteomes of mesothelioma and lung adenocarcinoma patients to identify novel soluble mesothelioma biomarkers. We performed quantitative mass-spectrometry-based proteomics using isobaric tags for quantification and used narrow-range immobilized pH gradient/high-resolution isoelectric focusing (pH 4-4.25) prior to analysis by means of nano liquid chromatography coupled to MS/MS. More than 1,300 proteins were identified in pleural effusions from patients with malignant mesothelioma (n = 6), lung adenocarcinoma (n = 6), or benign mesotheliosis (n = 7). Data are available via ProteomeXchange with identifier PXD000531. The identified proteins included a set of known mesothelioma markers and proteins that regulate hallmarks of cancer such as invasion, angiogenesis, and immune evasion, plus several new candidate proteins. Seven candidates (aldo-keto reductase 1B10, apolipoprotein C-I, galectin 1, myosin-VIIb, superoxide dismutase 2, tenascin C, and thrombospondin 1) were validated by enzyme-linked immunosorbent assays in a larger group of patients with mesothelioma (n = 37) or metastatic carcinomas (n = 25) and in effusions from patients with benign, reactive conditions (n = 16). Galectin 1 was identified as overexpressed in effusions from lung adenocarcinoma relative to mesothelioma and was validated as an excellent predictor for metastatic carcinomas against malignant mesothelioma. Galectin 1, aldo-keto reductase 1B10, and apolipoprotein C-I were all identified as potential prognostic biomarkers for malignant mesothelioma. This analysis of the effusion proteome

  6. Identification of potential prognostic microRNA biomarkers for predicting survival in patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Liao X

    2018-04-01

    Full Text Available Xiwen Liao,1 Guangzhi Zhu,1 Rui Huang,2 Chengkun Yang,1 Xiangkun Wang,1 Ketuan Huang,1 Tingdong Yu,1 Chuangye Han,1 Hao Su,1 Tao Peng1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China Background: The aim of the present study was to identify potential prognostic microRNA (miRNA biomarkers for hepatocellular carcinoma (HCC prognosis prediction based on a dataset from The Cancer Genome Atlas (TCGA. Materials and methods: A miRNA sequencing dataset and corresponding clinical parameters of HCC were obtained from TCGA. Genome-wide univariate Cox regression analysis was used to screen prognostic differentially expressed miRNAs (DEMs, and multivariable Cox regression analysis was used for prognostic signature construction. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature. Results: Five miRNAs were regarded as prognostic DEMs and used for prognostic signature construction. The five-DEM prognostic signature performed well in prognosis prediction (adjusted P < 0.0001, adjusted hazard ratio = 2.249, 95% confidence interval =1.491–3.394, and time-dependent receiver–operating characteristic (ROC analysis showed an area under the curve (AUC of 0.765, 0.745, 0.725, and 0.687 for 1-, 2-, 3-, and 5-year HCC overall survival (OS prediction, respectively. Comprehensive survival analysis of the prognostic signature suggests that the risk score model could serve as an independent factor of HCC and perform better in prognosis prediction than other traditional clinical indicators. Functional assessment of the target genes of hsa-mir-139 and hsa-mir-5003 indicates that they were significantly enriched in multiple biological processes and pathways, including cell proliferation and cell migration

  7. Clinical implications of six inflammatory biomarkers as prognostic indicators in Ewing sarcoma

    Directory of Open Access Journals (Sweden)

    Li YJ

    2017-09-01

    Full Text Available Yong-Jiang Li, Xi Yang, Wen-Biao Zhang, Cheng Yi, Feng Wang, Ping Li Department of Oncology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Abstract: Cancer-related systemic inflammation responses have been correlated with cancer development and progression. The prognostic significance of several inflammatory indicators, including neutrophil–lymphocyte ratio (NLR, platelet–lymphocyte ratio (PLR, Glasgow Prognostic Score (GPS, C-reactive protein to albumin ratio (CRP/Alb ratio, lymphocyte–monocyte ratio (LMR, and neutrophil–platelet score (NPS, were found to be correlated with prognosis in several cancers. However, the prognostic role of these inflammatory biomarkers in Ewing sarcoma has not been evaluated. This study enrolled 122 Ewing patients. Receiver operating characteristic (ROC analysis was generated to determine optimal cutoff values; areas under the curves (AUCs were assessed to show the discriminatory ability of the biomarkers; Kaplan–Meier analysis was conducted to plot the survival curves; and Cox multivariate survival analysis was performed to identify independent prognostic factors. The optimal cutoff values of CRP/Alb ratio, NLR, PLR, and LMR were 0.225, 2.38, 131, and 4.41, respectively. CRP/Alb ratio had a significantly larger AUC than NLR, PLR, LMR, and NPS. Higher levels of CRP/Alb ratio (hazard ratio [HR] 2.41, P=0.005, GPS (HR 2.27, P=0.006, NLR (HR 2.07, P=0.013, and PLR (HR 1.85, P=0.032 were significantly correlated with poor prognosis. As the biomarkers had internal correlations, only the CRP/Alb ratio was involved in the multivariate Cox analysis and remained an independent prognostic indicator. The study demonstrated that CRP/Alb ratio, GPS, and NLR were effective prognostic indicators for patients with Ewing sarcoma, and the CRP/Alb ratio was the most robust prognostic indicator with a discriminatory ability superior to that of the other indicators; however, PLR, LMR, and

  8. Prognostic Biomarker Identification Through Integrating the Gene Signatures of Hepatocellular Carcinoma Properties

    Directory of Open Access Journals (Sweden)

    Jialin Cai

    2017-05-01

    Full Text Available Many molecular classification and prognostic gene signatures for hepatocellular carcinoma (HCC patients have been established based on genome-wide gene expression profiling; however, their generalizability is unclear. Herein, we systematically assessed the prognostic effects of these gene signatures and identified valuable prognostic biomarkers by integrating these gene signatures. With two independent HCC datasets (GSE14520, N = 242 and GSE54236, N = 78, 30 published gene signatures were evaluated, and 11 were significantly associated with the overall survival (OS of postoperative HCC patients in both datasets. The random survival forest models suggested that the gene signatures were superior to clinical characteristics for predicting the prognosis of the patients. Based on the 11 gene signatures, a functional protein-protein interaction (PPI network with 1406 nodes and 10,135 edges was established. With tissue microarrays of HCC patients (N = 60, we determined the prognostic values of the core genes in the network and found that RAD21, CDK1, and HDAC2 expression levels were negatively associated with OS for HCC patients. The multivariate Cox regression analyses suggested that CDK1 was an independent prognostic factor, which was validated in an independent case cohort (N = 78. In cellular models, inhibition of CDK1 by siRNA or a specific inhibitor, RO-3306, reduced cellular proliferation and viability for HCC cells. These results suggest that the prognostic predictive capacities of these gene signatures are reproducible and that CDK1 is a potential prognostic biomarker or therapeutic target for HCC patients.

  9. LGE Provides Incremental Prognostic Information Over Serum Biomarkers in AL Cardiac Amyloidosis.

    Science.gov (United States)

    Boynton, Samuel J; Geske, Jeffrey B; Dispenzieri, Angela; Syed, Imran S; Hanson, Theodore J; Grogan, Martha; Araoz, Philip A

    2016-06-01

    This study sought to determine the prognostic value of cardiac magnetic resonance (CMR) late gadolinium enhancement (LGE) in amyloid light chain (AL) cardiac amyloidosis. Cardiac involvement is the major determinant of mortality in AL amyloidosis. CMR LGE is a marker of amyloid infiltration of the myocardium. The purpose of this study was to evaluate retrospectively the prognostic value of CMR LGE for determining all-cause mortality in AL amyloidosis and to compare the prognostic power with the biomarker stage. Seventy-six patients with histologically proven AL amyloidosis underwent CMR LGE imaging. LGE was categorized as global, focal patchy, or none. Global LGE was considered present if it was visualized on LGE images or if the myocardium nulled before the blood pool on a cine multiple inversion time (TI) sequence. CMR morphologic and functional evaluation, echocardiographic diastolic evaluation, and cardiac biomarker staging were also performed. Subjects' charts were reviewed for all-cause mortality. Cox proportional hazards analysis was used to evaluate survival in univariate and multivariate analysis. There were 40 deaths, and the median study follow-up period was 34.4 months. Global LGE was associated with all-cause mortality in univariate analysis (hazard ratio = 2.93; p < 0.001). In multivariate modeling with biomarker stage, global LGE remained prognostic (hazard ratio = 2.43; p = 0.01). Diffuse LGE provides incremental prognosis over cardiac biomarker stage in patients with AL cardiac amyloidosis. Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  10. Urine Trefoil Factors as Prognostic Biomarkers in Chronic Kidney Disease.

    Science.gov (United States)

    Yamanari, Toshio; Sugiyama, Hitoshi; Tanaka, Keiko; Morinaga, Hiroshi; Kitagawa, Masashi; Onishi, Akifumi; Ogawa-Akiyama, Ayu; Kano, Yuzuki; Mise, Koki; Ohmoto, Yasukazu; Shikata, Kenichi; Wada, Jun

    2018-01-01

    Trefoil factor family (TFF) peptides are increased in serum and urine in patients with chronic kidney disease (CKD). However, whether the levels of TFF predict the progression of CKD remains to be elucidated. We determined the TFF levels using peptide-specific ELISA in spot urine samples and performed a prospective cohort study. The association between the levels of urine TFFs and other urine biomarkers as well as the renal prognosis was analyzed in 216 CKD patients (mean age: 53.7 years, 47.7% female, 56.9% with chronic glomerulonephritis, and mean eGFR: 58.5 ml/min/1.73 m 2 ). The urine TFF1 and TFF3 levels significantly increased with the progression of CKD stages, but not the urine TFF2 levels. The TFF1 and TFF3 peptide levels predicted the progression of CKD ≥ stage 3b by ROC analysis (AUC 0.750 and 0.879, resp.); however, TFF3 alone predicted CKD progression in a multivariate logistic regression analysis (odds ratio 3.854, 95% confidence interval 1.316-11.55). The Kaplan-Meier survival curves demonstrated that patients with a higher TFF1 and TFF3 alone, or in combination with macroalbuminuria, had a significantly worse renal prognosis. The data suggested that urine TFF peptides are associated with renal progression and the outcomes in patients with CKD.

  11. Prognostic clinical and molecular biomarkers of renal disease in type 2 diabetes

    DEFF Research Database (Denmark)

    Pena, Michelle J; de Zeeuw, Dick; Mischak, Harald

    2015-01-01

    biomarkers address the predictive performance of novel biomarker panels in addition to the classical panel in type 2 diabetes. However, the prospective studies conducted so far have small sample sizes, are insufficiently powered and lack external validation. Adequately sized validation studies of multiple......Diabetic kidney disease occurs in ∼ 25-40% of patients with type 2 diabetes. Given the high risk of progressive renal function loss and end-stage renal disease, early identification of patients with a renal risk is important. Novel biomarkers may aid in improving renal risk stratification...... and metabolomics biomarkers. We focus on multiple biomarker panels since the molecular processes of renal disease progression in type 2 diabetes are heterogeneous, rendering it unlikely that a single biomarker significantly adds to clinical risk prediction. A limited number of prospective studies of multiple...

  12. Prognostic nutritional index as a prognostic biomarker for survival in digestive system carcinomas.

    Science.gov (United States)

    Zhao, Yang; Xu, Peng; Kang, Huafeng; Lin, Shuai; Wang, Meng; Yang, Pengtao; Dai, Cong; Liu, Xinghan; Liu, Kang; Zheng, Yi; Dai, Zhijun

    2016-12-27

    The prognostic nutritional index (PNI) has been reported to correlate with the prognosis in patients with various malignancies. We performed a meta-analysis to determine the predictive potential of PNI in digestive system cancers. Twenty-three studies with a total of 7,384 patients suffering from digestive system carcinomas were involved in this meta-analysis. A lower PNI was significantly associated with the shorter overall survival (OS) [Hazard Ratio (HR) 1.83, 95% Confidence Interval (CI) 1.62-2.07], the poorer disease-free survival (DFS) (HR 1.85, 95% CI 1.19-2.89), and the higher rate of post-operative complications (HR 2.31, 95% CI 1.63-3.28). In conclusion, PNI was allowed to function as an efficient indicator for the prognosis of patients with digestive system carcinomas.

  13. Characterization of KIF11 as a novel prognostic biomarker and therapeutic target for oral cancer.

    Science.gov (United States)

    Daigo, Kayo; Takano, Atsushi; Thang, Phung Manh; Yoshitake, Yoshihiro; Shinohara, Masanori; Tohnai, Iwau; Murakami, Yoshinori; Maegawa, Jiro; Daigo, Yataro

    2018-01-01

    Oral cancer has a high mortality rate, and its incidence is increasing gradually worldwide. As the effectiveness of standard treatments is still limited, the development of new therapeutic strategies is eagerly awaited. Kinesin family member 11 (KIF11) is a motor protein required for establishing a bipolar spindle in cell division. The role of KIF11 in oral cancer is unclear. Therefore, the present study aimed to assess the role of KIF11 in oral cancer and evaluate its role as a prognostic biomarker and therapeutic target for treating oral cancer. Immunohistochemical analysis demonstrated that KIF11 was expressed in 64 of 99 (64.6%) oral cancer tissues but not in healthy oral epithelia. Strong KIF11 expression was significantly associated with poor prognosis among oral cancer patients (P=0.034), and multivariate analysis confirmed its independent prognostic value. In addition, inhibition of KIF11 expression by transfection of siRNAs into oral cancer cells or treatment of cells with a KIF11 inhibitor significantly suppressed cell proliferation, probably through G2/M arrest and subsequent induction of apoptosis. These results suggest that KIF11 could be a potential prognostic biomarker and therapeutic target for oral cancer.

  14. CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Rossi, Daniela; Volanti, Paolo; Brambilla, Liliana; Colletti, Tiziana; Spataro, Rossella; La Bella, Vincenzo

    2018-03-01

    Elevated cerebrospinal fluid (CSF), Neurofilament Light (NF-L) and phosphorylated Heavy (pNF-H) chain levels have been found in Amyotrophic Lateral Sclerosis (ALS), with studies reporting a correlation of both neurofilaments (NFs) with the disease progression. Here, we measured NF-L and pNF-H concentrations in the CSF of ALS patients from a single tertiary Center and investigated their relationship with disease-related variables. A total of 190 ALS patients (Bulbar, 29.9%; Spinal, 70.1%; M/F = 1.53) and 130 controls with mixed neurological diseases were recruited. Demographic and clinical variables were recorded, and ΔFS was used to rate the disease progression. Controls were divided into two cohorts: (1) patients with non-inflammatory neurological diseases (CTL-1); (2) patients with acute/subacute inflammatory diseases and tumors, expected to lead to significant axonal and tissue damage (CTL-2). For each patient and control, CSF was taken at the time of the diagnostic work-up and stored following the published guidelines. CSF NF-L and pNF-H were assayed with commercially available ELISA-based methods. Standard curves (from independent ELISA kits) were highly reproducible for both NFs, with a coefficient of variation CSF NF-L and pNF-H levels in ALS were significantly increased when compared to CTL-1 (NF-L: ALS, 4.7 ng/ml vs CTL-1, 0.61 ng/ml, p CSF NF-L and pNF-H represent valuable diagnostic and prognostic biomarkers in ALS.

  15. Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection.

    Science.gov (United States)

    Higashikawa, Toshihiro; Okuro, Masashi; Ishigami, Keiichirou; Mae, Kunihiro; Sangen, Ryusho; Mizuno, Takurou; Usuda, Daisuke; Saito, Atushi; Kasamaki, Yuji; Fukuda, Akihiro; Saito, Hitoshi; Morimoto, Shigeto; Kanda, Tsugiyasu

    2018-01-01

    Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.

  16. Systematic Evaluation of the Prognostic Impact and Intratumour Heterogeneity of Clear Cell Renal Cell Carcinoma Biomarkers

    DEFF Research Database (Denmark)

    Gulati, Sakshi; Martinez, Pierre; Joshi, Tejal

    2014-01-01

    and statistical analysisBiomarker association with CSS was analysed by univariate and multivariate analyses. Results and limitationsA total of 17 of 28 biomarkers (TP53 mutations; amplifications of chromosomes 8q, 12, 20q11.21q13.32, and 20 and deletions of 4p, 9p, 9p21.3p24.1, and 22q; low EDNRB and TSPAN7...... expression and six gene expression signatures) were validated as predictors of poor CSS in univariate analysis. Tumour stage and the ccB expression signature were the only independent predictors in multivariate analysis. ITH of the ccB signature was identified in 8 of 10 tumours. Several genetic alterations...... that were significant in univariate analysis were enriched, and chromosomal instability indices were increased in samples expressing the ccB signature. The study may be underpowered to validate low-prevalence biomarkers. ConclusionsThe ccB signature was the only independent prognostic biomarker. Enrichment...

  17. Investigation of p16(INK4a) as a prognostic biomarker in oral epithelial dysplasia.

    Science.gov (United States)

    Nankivell, Paul; Williams, Hazel; Webster, Keith; Pearson, David; High, Alec; MacLennan, Kenneth; Senguven, Burcu; McConkey, Christopher; Rabbitts, Pamela; Mehanna, Hisham

    2014-04-01

    Human papilloma virus is a risk factor for oropharyngeal cancer. Evidence for a similar aetiological role in the development of oral dysplasia or its transformation to oral cancer is not as clear. Meta-analyses estimate the prevalence of high-risk human papilloma virus (HPV) serotypes to be three times higher in pre-malignant lesions and cancer than in normal oral mucosa. However, this does not imply a causal relationship. Conflicting results are reported from the few studies examining the prognostic significance of HPV positivity in the development of oral cancer. We aimed to examine the ability of p16(INK4a) protein expression, a surrogate marker of HPV infection, to predict malignant progression in a large cohort of oral dysplasia patients. One hundred forty eight oral dysplasia cases underwent immunohistochemical analysis using a monoclonal antibody against p16(INK4a) . Clinical factors were also collated on each case. Slides were double scored independently by two trained observers. Univariate analyses using both logistic and Cox regression models were performed. Thirty nine of 148 cases progressed to cancer. Ten of 148 cases (7%) were p16(INK4a) positive. High grade of dysplasia (P = 0.0002) and lesion morphology (P = 0.03) were found to be prognostic of malignant progression. p16(INK4a) score was not prognostic in this cohort (P = 0.29). This did not change with a time to event analysis (P = 0.24). Few studies have assessed the aetiological role of HPV in cancer development from dysplastic lesions. Our study, using one of the largest cohorts of oral dysplasia, demonstrated a low rate of p16(INK4a) positivity and was unable to confirm a prognostic ability for this biomarker. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. An exploratory study of inflammatory cytokines as prognostic biomarkers in patients with ductal pancreatic adenocarcinoma.

    Science.gov (United States)

    Dima, Simona O; Tanase, Cristiana; Albulescu, Radu; Herlea, Vlad; Chivu-Economescu, Mihaela; Purnichescu-Purtan, Raluca; Dumitrascu, Traian; Duda, Dan G; Popescu, Irinel

    2012-10-01

    We measured the serum concentration of a panel of inflammatory cytokines and evaluated their association with circulating proangiogenic biomarkers and with outcome in patients with pancreatic ductal adenocarcinoma (PDAC). We collected serum samples from 36 patients with PDAC, 9 patients with chronic pancreatitis, and 22 healthy volunteers as a control. Inflammatory cytokines and proangiogenic biomarkers were measured using the multianalyte xMAP array and carcinoembryonic antigen (CEA) and carbohydrate 19-9 by immunoassay. Patients with PDAC had higher circulating levels of interleukin 6 (IL-6) than those of patients with pancreatitis or healthy individuals and higher levels of IL-10 and tumor necrosis factor α (TNF-α) compared with those of healthy individuals. In patients with PDAC, circulating IL-6, TNF-α, IL-1β, and IL-10 correlated with serum concentrations of vascular endothelial growth factor and basic fibroblast growth factor; circulating IL-6, IL-1β, and TNF-α correlated with carbohydrate 19-9; and IL-8, IL-10, and TNF-α correlated with CEA levels. Circulating IL-8, TNF-α, and CEA; tumor stage; and lymph node metastases were associated with a poor outcome. The results of this exploratory study indicate that inflammatory cytokines should be pursued as potential prognostic biomarkers as well as targets for therapy in larger studies in PDAC.

  19. Modern molecular biomarkers of head and neck cancer. Part I. Epigenetic diagnostics and prognostics: Systematic review.

    Science.gov (United States)

    Juodzbalys, Gintaras; Kasradze, David; Cicciù, Marco; Sudeikis, Aurimas; Banys, Laurynas; Galindo-Moreno, Pablo; Guobis, Zygimantas

    2016-01-01

    Nearly half of the head and neck cancer cases are diagnosed in late stages. Traditional screening modalities have many disadvantages. The aim of the present article was to review the scientific literature about novel head and neck cancer diagnostics - epigenetic biomarkers. A comprehensive review of the current literature was conducted according to the PRISMA guidelines by accessing the NCBI PubMed database. Authors conducted the search of articles in English language published from 2004 to 2015. A total of thirty three relevant studies were included in the review. Fifteen of them concerned DNA methylation alterations, nine evaluation of abundancies in histone expressions and nine miRNA expression changes in HNC. Considerable number of epigenetic biomarkers have been identified in both tumor tissue and salivary samples. Genes with best diagnostic effectiveness rates and further studying prospects were: TIMP3, DCC, DAPK, CDH1, CCNA1, AIM1, MGMT, HIC1, PAX1, PAX5, ZIC4, p16, EDNRB, KIF1A, MINT31, CD44, RARβ , ECAD. Individual histone and miRNA alterations tend to be hnc specific. Prognostic values of separate biomarkers are ambiguous. No established standards for molecular assay of head and neck cancer was found in order to elude the paradoxical results and discrepancies in separate trials.

  20. S100A14 is a novel independent prognostic biomarker in the triple-negative breast cancer subtype

    DEFF Research Database (Denmark)

    Ehmsen, Sidse; Hansen, Lea Tykgaard; Bak, Martin

    2015-01-01

    Triple-negative breast cancer (TNBC) represents a heterogeneous subgroup with generally poor outcome and lack of an effective targeted therapy. Prognostic or predictive biomarkers to guide treatment decisions for this group of patients are needed. To evaluate the potential of S100A14 protein...... as a novel biomarker in TNBC, the protein expression of S100A14 was correlated with clinical outcomes in a Pilot Sample set and a Danish cohort of predominantly TNBC patients. Kaplan-Meier analysis identified a prognostic impact of S100A14 on disease-free survival and overall survival, showing that tumors......-), had equally poor outcomes as those with tumor-positive axillary lymph nodes (N+), while TNBC/N- patients with low S100A14 expression had a significantly better disease free survival (p = 0.013). Multivariate analysis revealed that S100A14 is an independent prognostic factor for TNBC patients (p = 0...

  1. Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

    Science.gov (United States)

    Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

    2012-01-17

    This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  2. UCH-LI acts as a novel prognostic biomarker in gastric cardiac adenocarcinoma.

    Science.gov (United States)

    Yang, Honghong; Zhang, Chunhong; Fang, Shan; Ou, Rongying; Li, Wenfeng; Xu, Yunsheng

    2015-01-01

    Gastric cardiac adenocarcinoma (GCA) accounts for a majority of gastric cancer population and harbors unfavorable outcome. Ubiquitin C-terminal hydrolase L1 (UCH-L1) belongs to the deubiquitinating enzyme family, which could regulate cell growth in human cancers. In the present study, expression of UCH-L1 was evaluated in 196 GCAs by immunohistochemistry using tissue microarray and its function on gastric cancer cells was measured. UCH-L1 expression was increased in GCA specimens, compared with their normal tissues and UCH-L1 overexpression is tightly correlated with tumor size and overall TNM stage. Log-rank analysis showed that UCH-L1 positive is reversely associated with cumulative survival (Pstage that is a known negative factor in gastric cancers (Hazard Ratio=0.33, Pgastric cancer cells. Our findings suggest that UCH-L1 is a promising prognostic biomarker for GCAs and might play an important role in the carcinogenesis of gastric cancer.

  3. Cerebrospinal fluid chitinase-3-like 2 and chitotriosidase are potential prognostic biomarkers in early multiple sclerosis

    DEFF Research Database (Denmark)

    Møllgaard, M; Degn, M; Sellebjerg, F

    2016-01-01

    : In a prospective cohort of 73 patients with ON as a first demyelinating episode and 26 age-matched healthy controls levels of CHI3L2 and chitotriosidase in CSF were explored by enzyme-linked immunosorbent assay. Associations with magnetic resonance imaging white matter lesions, CSF oligoclonal bands......BACKGROUND AND PURPOSE: The role of chitinases and chitinase-like proteins in multiple sclerosis (MS) is currently unknown; however, cerebrospinal fluid (CSF) levels of chitinase 3-like 1 (CHI3L1) predict prognosis in early MS. Whether this applies to other chitinases and chitinase-like proteins...... is yet to be established. Our objective was to investigate the potential of chitinase 3-like 2 (CHI3L2) and chitotriosidase as prognostic biomarkers in optic neuritis (ON) as the first demyelinating episode and to evaluate the ability of CHI3L2 to predict long-term MS risk and disability. METHODS...

  4. F11R is a novel monocyte prognostic biomarker for malignant glioma.

    Directory of Open Access Journals (Sweden)

    Winnie W Pong

    Full Text Available Brain tumors (gliomas contain large populations of infiltrating macrophages and recruited microglia, which in experimental murine glioma models promote tumor formation and progression. Among the barriers to understanding the contributions of these stromal elements to high-grade glioma (glioblastoma; GBM biology is the relative paucity of tools to characterize infiltrating macrophages and resident microglia. In this study, we leveraged multiple RNA analysis platforms to identify new monocyte markers relevant to GBM patient outcome.High-confidence lists of mouse resident microglia- and bone marrow-derived macrophage-specific transcripts were generated using converging RNA-seq and microarray technologies and validated using qRT-PCR and flow cytometry. Expression of select cell surface markers was analyzed in brain-infiltrating macrophages and resident microglia in an induced GBM mouse model, while allogeneic bone marrow transplantation was performed to trace the origins of infiltrating and resident macrophages. Glioma tissue microarrays were examined by immunohistochemistry, and the Gene Expression Omnibus (GEO database was queried to determine the prognostic value of identified microglia biomarkers in human GBM.We generated a unique catalog of differentially-expressed bone marrow-derived monocyte and resident microglia transcripts, and demonstrated that brain-infiltrating macrophages acquire F11R expression in GBM and following bone-marrow transplantation. Moreover, mononuclear cell F11R expression positively correlates with human high-grade glioma and additionally serves as a biomarker for GBM patient survival, regardless of GBM molecular subtype.These studies establish F11R as a novel monocyte prognostic marker for GBM critical for defining a subpopulation of stromal cells for future potential therapeutic intervention.

  5. Discovery of prognostic biomarker candidates of lacunar infarction by quantitative proteomics of microvesicles enriched plasma.

    Directory of Open Access Journals (Sweden)

    Arnab Datta

    Full Text Available Lacunar infarction (LACI is a subtype of acute ischemic stroke affecting around 25% of all ischemic stroke cases. Despite having an excellent recovery during acute phase, certain LACI patients have poor mid- to long-term prognosis due to the recurrence of vascular events or a decline in cognitive functions. Hence, blood-based biomarkers could be complementary prognostic and research tools.Plasma was collected from forty five patients following a non-disabling LACI along with seventeen matched control subjects. The LACI patients were monitored prospectively for up to five years for the occurrence of adverse outcomes and grouped accordingly (i.e., LACI-no adverse outcome, LACI-recurrent vascular event, and LACI-cognitive decline without any recurrence of vascular events. Microvesicles-enriched fractions isolated from the pooled plasma of four groups were profiled by an iTRAQ-guided discovery approach to quantify the differential proteome. The data have been deposited to the ProteomeXchange with identifier PXD000748. Bioinformatics analysis and data mining revealed up-regulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A while albumin was down-regulated in both groups of patients with adverse outcome.This data set may offer important insight into the mechanisms of poor prognosis and provide candidate prognostic biomarkers for validation on larger cohort of individual LACI patients.

  6. EMMPRIN/CD147 is an independent prognostic biomarker in cutaneous melanoma.

    Science.gov (United States)

    Caudron, Anne; Battistella, Maxime; Feugeas, Jean-Paul; Pages, Cécile; Basset-Seguin, Nicole; Mazouz Dorval, Sarra; Funck Brentano, Elisa; Sadoux, Aurélie; Podgorniak, Marie-Pierre; Menashi, Suzanne; Janin, Anne; Lebbé, Céleste; Mourah, Samia

    2016-08-01

    CD147 has been implicated in melanoma invasion and metastasis mainly through increasing metalloproteinase synthesis and regulating VEGF/VEGFR signalling. In this study, the prognostic value of CD147 expression was investigated in a cohort of 196 cutaneous melanomas including 136 consecutive primary malignant melanomas, 30 lymph nodes, 16 in-transit and 14 visceral metastases. A series of 10 normal skin, 10 blue nevi and 10 dermal nevi was used as control. CD147 expression was assessed by immunohistochemistry, and the association of its expression with the clinicopathological characteristics of patients and survival was evaluated using univariate and multivariate statistical analyses. Univariate analysis showed that high CD147 expression was significantly associated with metastatic potential and with a reduced overall survival (P CD147 expression level was correlated with histological factors which were associated with prognosis: Clark level, ulceration status and more particularly with Breslow index (r = 0.7, P CD147 expression level and ulceration status as predicting factors for metastasis and overall survival (P CD147 emerges as an important factor in the aggressive behaviour of melanoma and deserves further evaluation as an independent prognostic biomarker. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Differentially regulated miRNAs as prognostic biomarkers in the blood of primary CNS lymphoma patients.

    Science.gov (United States)

    Roth, Patrick; Keller, Andreas; Hoheisel, Jörg D; Codo, Paula; Bauer, Andrea S; Backes, Christina; Leidinger, Petra; Meese, Eckart; Thiel, Eckhard; Korfel, Agnieszka; Weller, Michael

    2015-02-01

    Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short- and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

    Science.gov (United States)

    Lou, Sha; Balluff, Benjamin; Cleven, Arjen H. G.; Bovée, Judith V. M. G.; McDonnell, Liam A.

    2017-02-01

    Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival ( m/z 180.9436 and 241.0118) and metastasis-free survival ( m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

  9. Serum C-Reactive Protein as a Prognostic Biomarker in Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Lizio, Andrea; Maestri, Eleonora; Sansone, Valeria Ada; Mora, Gabriele; Miller, Robert G.; Appel, Stanley H.; Chiò, Adriano

    2017-01-01

    Importance Various factors have been proposed as possible candidates associated with the prognosis of amyotrophic lateral sclerosis (ALS); however, there is still no consensus on which biomarkers are reliable prognostic factors. C-reactive protein (CRP) is a biomarker of the inflammatory response that shows significant prognostic value for several diseases. Objective To examine the prognostic significance of CRP in ALS. Design, Setting, and Participants Patients’ serum CRP levels were evaluated from January 1, 2009, to June 30, 2015, in a large cohort of patients with ALS observed by an Italian tertiary multidisciplinary center. Results were replicated in an independent cohort obtained from a population-based registry of patients with ALS. A post hoc analysis was performed of the phase 2 trial of NP001 to determine whether stratification by levels of CRP improves differentiation of responders and nonresponders to the drug. Main Outcomes and Measures Serum CRP levels from the first examination were recorded to assess their effect on disease progression and survival. Results A total of 394 patients with ALS (168 women and 226 men; mean [SD] age at diagnosis, 60.18 [13.60] years) were observed in a tertiary multidisciplinary center, and the analysis was replicated in an independent cohort of 116 patients with ALS (50 women and 66 men; mean [SD] age at diagnosis, 67.00 [10.74] years) identified through a regional population-based registry. Serum CRP levels in the 394 patients with ALS correlated with severity of functional impairment, as measured by total score on the ALS Functional Rating Scale–Revised, at first evaluation (r = –0.14818; P = .004), and with patient survival (hazard ratio, 1.129; 95% CI, 1.033-1.234; P = .007). Similar results were found in the independent cohort (hazard ratio, 1.044; 95% CI, 1.016-1.056; P ≤ .001). Moreover, a post hoc analysis of the phase 2 trial of NP001 using the same CRP threshold showed that patients with

  10. Prognostic value of liver fibrosis and steatosis biomarkers in type-2 diabetes and dyslipidaemia.

    Science.gov (United States)

    Perazzo, H; Munteanu, M; Ngo, Y; Lebray, P; Seurat, N; Rutka, F; Couteau, M; Jacqueminet, S; Giral, P; Monneret, D; Imbert-Bismut, F; Ratziu, V; Hartemann-Huertier, A; Housset, C; Poynard, T

    2014-11-01

    In cardiometabolic disorders, non-alcoholic fatty liver disease is frequent and presumably associated with increased mortality and cardiovascular risk. To evaluate the prognostic value of non-invasive biomarkers of liver fibrosis (FibroTest) and steatosis (SteatoTest) in patients with type-2 diabetes and/or dyslipidaemia. A total of 2312 patients with type-2 diabetes and/or dyslipidaemia were included and prospectively followed up for 5-15 years. The cardiovascular Framingham-risk score was calculated; advanced fibrosis and severe steatosis, were defined by FibroTest >0.48 and SteatoTest >0.69, respectively, as previously established. During a median follow-up of 12 years, 172 patients (7.4%) died. The leading causes of mortality were cancer (31%) and cardiovascular-related death (20%). The presence of advanced fibrosis [HR (95% CI)] [2.98 (95% CI 1.78-4.99); P < 0.0001] or severe steatosis [1.86 (1.34-2.58); P = 0.0002] was associated with an increased risk of mortality. In a multivariate Cox model adjusted for confounders: the presence of advanced fibrosis was associated with overall mortality [1.95 (1.12-3.41); P = 0.02]; advanced fibrosis at baseline [n = 50/677; 1.92 (1.04-3.55); P = 0.04] and progression to advanced fibrosis during follow-up [n = 16/127; 4.8 (1.5-14.9); P = 0.007] were predictors of cardiovascular events in patients with type-2 diabetes. In patients with a Framingham-risk score ≥20%, the presence of advanced fibrosis was predictive of cardiovascular events [2.24 (1.16-4.33); P < 0.05]. Liver biomarkers, such as FibroTest and SteatoTest, have prognostic values in patients with metabolic disorders. FibroTest has prognostic value for predicting overall survival in patients with type-2 diabetes and/or dyslipidaemia. In type-2 diabetes, FibroTest predicted cardiovascular events and improved the Framingham-risk score. © 2014 John Wiley & Sons Ltd.

  11. Diagnosing phenotypes of single-sample individuals by edge biomarkers.

    Science.gov (United States)

    Zhang, Wanwei; Zeng, Tao; Liu, Xiaoping; Chen, Luonan

    2015-06-01

    Network or edge biomarkers are a reliable form to characterize phenotypes or diseases. However, obtaining edges or correlations between molecules for an individual requires measurement of multiple samples of that individual, which are generally unavailable in clinical practice. Thus, it is strongly demanded to diagnose a disease by edge or network biomarkers in one-sample-for-one-individual context. Here, we developed a new computational framework, EdgeBiomarker, to integrate edge and node biomarkers to diagnose phenotype of each single test sample. By applying the method to datasets of lung and breast cancer, it reveals new marker genes/gene-pairs and related sub-networks for distinguishing earlier and advanced cancer stages. Our method shows advantages over traditional methods: (i) edge biomarkers extracted from non-differentially expressed genes achieve better cross-validation accuracy of diagnosis than molecule or node biomarkers from differentially expressed genes, suggesting that certain pathogenic information is only present at the level of network and under-estimated by traditional methods; (ii) edge biomarkers categorize patients into low/high survival rate in a more reliable manner; (iii) edge biomarkers are significantly enriched in relevant biological functions or pathways, implying that the association changes in a network, rather than expression changes in individual molecules, tend to be causally related to cancer development. The new framework of edge biomarkers paves the way for diagnosing diseases and analyzing their molecular mechanisms by edges or networks in one-sample-for-one-individual basis. This also provides a powerful tool for precision medicine or big-data medicine. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  12. SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

    International Nuclear Information System (INIS)

    Alsbeih, Ghazi; El-Sebaie, Medhat; Al-Harbi, Najla; Al-Hadyan, Khaled; Shoukri, Mohamed; Al-Rajhi, Nasser

    2013-01-01

    Biomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients. A cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Univariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs. Univariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy

  13. Identification and Validation of a Diagnostic and Prognostic Multi-Gene Biomarker Panel for Pancreatic Ductal Adenocarcinoma.

    Science.gov (United States)

    Klett, Hagen; Fuellgraf, Hannah; Levit-Zerdoun, Ella; Hussung, Saskia; Kowar, Silke; Küsters, Simon; Bronsert, Peter; Werner, Martin; Wittel, Uwe; Fritsch, Ralph; Busch, Hauke; Boerries, Melanie

    2018-01-01

    Late diagnosis and systemic dissemination essentially contribute to the invariably poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Therefore, the development of diagnostic biomarkers for PDAC are urgently needed to improve patient stratification and outcome in the clinic. By studying the transcriptomes of independent PDAC patient cohorts of tumor and non-tumor tissues, we identified 81 robustly regulated genes, through a novel, generally applicable meta-analysis. Using consensus clustering on co-expression values revealed four distinct clusters with genes originating from exocrine/endocrine pancreas, stromal and tumor cells. Three clusters were strongly associated with survival of PDAC patients based on TCGA database underlining the prognostic potential of the identified genes. With the added information of impact of survival and the robustness within the meta-analysis, we extracted a 17-gene subset for further validation. We show that it did not only discriminate PDAC from non-tumor tissue and stroma in fresh-frozen as well as formalin-fixed paraffin embedded samples, but also detected pancreatic precursor lesions and singled out pancreatitis samples. Moreover, the classifier discriminated PDAC from other cancers in the TCGA database. In addition, we experimentally validated the classifier in PDAC patients on transcript level using qPCR and exemplify the usage on protein level for three proteins (AHNAK2, LAMC2, TFF1) using immunohistochemistry and for two secreted proteins (TFF1, SERPINB5) using ELISA-based protein detection in blood-plasma. In conclusion, we present a novel robust diagnostic and prognostic gene signature for PDAC with future potential applicability in the clinic.

  14. Identification and Validation of a Diagnostic and Prognostic Multi-Gene Biomarker Panel for Pancreatic Ductal Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Hagen Klett

    2018-04-01

    Full Text Available Late diagnosis and systemic dissemination essentially contribute to the invariably poor prognosis of pancreatic ductal adenocarcinoma (PDAC. Therefore, the development of diagnostic biomarkers for PDAC are urgently needed to improve patient stratification and outcome in the clinic. By studying the transcriptomes of independent PDAC patient cohorts of tumor and non-tumor tissues, we identified 81 robustly regulated genes, through a novel, generally applicable meta-analysis. Using consensus clustering on co-expression values revealed four distinct clusters with genes originating from exocrine/endocrine pancreas, stromal and tumor cells. Three clusters were strongly associated with survival of PDAC patients based on TCGA database underlining the prognostic potential of the identified genes. With the added information of impact of survival and the robustness within the meta-analysis, we extracted a 17-gene subset for further validation. We show that it did not only discriminate PDAC from non-tumor tissue and stroma in fresh-frozen as well as formalin-fixed paraffin embedded samples, but also detected pancreatic precursor lesions and singled out pancreatitis samples. Moreover, the classifier discriminated PDAC from other cancers in the TCGA database. In addition, we experimentally validated the classifier in PDAC patients on transcript level using qPCR and exemplify the usage on protein level for three proteins (AHNAK2, LAMC2, TFF1 using immunohistochemistry and for two secreted proteins (TFF1, SERPINB5 using ELISA-based protein detection in blood-plasma. In conclusion, we present a novel robust diagnostic and prognostic gene signature for PDAC with future potential applicability in the clinic.

  15. Prognostics

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics has received considerable attention recently as an emerging sub-discipline within SHM. Prognosis is here strictly defined as “predicting the time at...

  16. Validation of the 18-gene classifier as a prognostic biomarker of distant metastasis in breast cancer.

    Directory of Open Access Journals (Sweden)

    Skye Hung-Chun Cheng

    Full Text Available We validated an 18-gene classifier (GC initially developed to predict local/regional recurrence after mastectomy in estimating distant metastasis risk. The 18-gene scoring algorithm defines scores as: <21, low risk; ≥21, high risk. Six hundred eighty-three patients with primary operable breast cancer and fresh frozen tumor tissues available were included. The primary outcome was the 5-year probability of freedom from distant metastasis (DMFP. Two external datasets were used to test the predictive accuracy of 18-GC. The 5-year rates of DMFP for patients classified as low-risk (n = 146, 21.7% and high-risk (n = 537, 78.6% were 96.2% (95% CI, 91.1%-98.8% and 80.9% (74.6%-81.9%, respectively (median follow-up interval, 71.8 months. The 5-year rates of DMFP of the low-risk group in stage I (n = 62, 35.6%, stage II (n = 66, 20.1%, and stage III (n = 18, 10.3% were 100%, 94.2% (78.5%-98.5%, and 90.9% (50.8%-98.7%, respectively. Multivariate analysis revealed that 18-GC is an independent prognostic factor of distant metastasis (adjusted hazard ratio, 5.1; 95% CI, 1.8-14.1; p = 0.0017 for scores of ≥21. External validation showed that the 5-year rate of DMFP in the low- and high-risk patients was 94.1% (82.9%-100% and 80.3% (70.7%-89.9%, p = 0.06 in a Singapore dataset, and 89.5% (81.9%-94.1% and 73.6% (67.2%-79.0%, p = 0.0039 in the GEO-GSE20685 dataset, respectively. In conclusion, 18-GC is a viable prognostic biomarker for breast cancer to estimate distant metastasis risk.

  17. Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.

    Science.gov (United States)

    Droop, Johanna; Szarvas, Tibor; Schulz, Wolfgang A; Niedworok, Christian; Niegisch, Günter; Scheckenbach, Kathrin; Hoffmann, Michèle J

    2017-01-01

    Many long noncoding RNAs (lncRNAs) are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC), several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1) was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106). Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252,) and correlation to overall survival (OS). All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could become useful to

  18. Prognostic value of molecular and imaging biomarkers in patients with supratentorial glioma

    Energy Technology Data Exchange (ETDEWEB)

    Lopci, Egesta [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Riva, Marco; Raneri, Fabio; Pessina, Federico [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Olivari, Laura; Rossi, Marco; Alfieri, Tommaso [Universita degli Studi di Milano, Milan (Italy); Soffietti, Riccardo; Ruda, Roberta [University and City of Health and Science Hospital, Neuro-Oncology, Turin (Italy); Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine, Genova (Italy); Bizzi, Alberto [Fondazione IRCCS Istituto Neurologico Carlo Besta, Neuroradiology, Milan (Italy); Navarria, Pierina; Ascolese, Anna Maria [Humanitas Clinical and Research Hospital, Radiosurgery and Radiotherapy, Rozzano, Milan (Italy); Fernandes, Bethania [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Grimaldi, Marco [Humanitas Clinical and Research Hospital, Medical Oncology, Rozzano, Milan (Italy); Simonelli, Matteo; Zucali, Paolo Andrea [Humanitas Clinical and Research Hospital, Radiology Department, Rozzano, Milan (Italy); Scorsetti, Marta [Humanitas Clinical and Research Hospital, Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Bello, Lorenzo [Humanitas Clinical and Research Hospital, Neurosurgery, Rozzano, Milan (Italy); Universita degli Studi di Milano, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine, Humanitas Cancer Center, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

    2017-07-15

    We evaluated the relationship between {sup 11}C-methionine PET ({sup 11}C-METH PET) findings and molecular biomarkers in patients with supratentorial glioma who underwent surgery. A consecutive series of 109 patients with pathologically proven glioma (64 men, 45 women; median age 43 years) referred to our Institution from March 2012 to January 2015 for tumour resection and who underwent preoperative {sup 11}C-METH PET were analysed. Semiquantitative evaluation of the {sup 11}C-METH PET images included SUVmax, region of interest-to-normal brain SUV ratio (SUVratio) and metabolic tumour volume (MTV). Imaging findings were correlated with disease outcome in terms of progression-free survival (PFS), and compared with other clinical biological data, including IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation. The patients were monitored for a mean period of 16.7 months (median 13 months). In all patients, the tumour was identified on {sup 11}C-METH PET. Significant differences in SUVmax, SUVratio and MTV were observed in relation to tumour grade (p < 0.001). IDH1 mutation was found in 49 patients, 1p/19q codeletion in 58 patients and MGMT promoter methylation in 74 patients. SUVmax and SUVratio were significantly inversely correlated with the presence of IDH1 mutation (p < 0.001). Using the 2016 WHO classification, SUVmax and SUVratio were significantly higher in patients with primary glioblastoma (IDH1-negative) than in those with other diffuse gliomas (p < 0.001). Relapse or progression was documented in 48 patients (median PFS 8.7 months). Cox regression analysis showed that SUVmax and SUVratio, tumour grade, tumour type on 2016 WHO classification, IDH1 mutation status, 1p/19q codeletion and MGMT promoter methylation were significantly associated with PFS. None of these factors was found to be an independent prognostic factor in multivariate analysis. {sup 11}C-METH PET parameters are significantly correlated with histological grade and IDH1

  19. Diagnostic and prognostic value of long noncoding RNAs as biomarkers in urothelial carcinoma.

    Directory of Open Access Journals (Sweden)

    Johanna Droop

    Full Text Available Many long noncoding RNAs (lncRNAs are deregulated in cancer and contribute to oncogenesis. In urothelial carcinoma (UC, several lncRNAs have been reported to be overexpressed and proposed as biomarkers. As most reports have not been confirmed independently in large tissue sets, we aimed to validate the diagnostic and prognostic value of lncRNA upregulation in independent cohorts of UC patients. Thus, expression of seven lncRNA candidates (GAS5, H19, linc-UBC1, MALAT1, ncRAN, TUG1, UCA1 was measured by RT-qPCR in cell lines and tissues and correlated to clinicopathological parameters including follow-up data (set 1: N n = 10; T n = 106. Additionally, publicly available TCGA data was investigated for differential expression in UC tissues (set 2: N n = 19; T n = 252, and correlation to overall survival (OS. All proposed candidates tended to be upregulated in tumour tissues, with the exception of MALAT1, which was rather diminished in cancer tissues of both data sets. However, strong overexpression was generally limited to individual tumour tissues and statistically significant overexpression was only observed for UCA1, TUG1, ncRAN and linc-UBC1 in tissue set 2, but for no candidate in set 1. Altered expression of individual lncRNAs was associated with overall survival, but not consistently between both patient cohorts. Interestingly, lower expression of TUG1 in a subset of UC patients with muscle-invasive tumours was significantly correlated with worse OS in both cohorts. Further analysis revealed that tumours with low TUG1 expression are characterized by a basal-squamous-like subtype signature accounting for the association with poor outcome. In conclusion, our study demonstrates that overexpression of the candidate lncRNAs is found in many UC cases, but does not occur consistently and strongly enough to provide reliable diagnostic or prognostic value as an individual biomarker. Subtype-dependent expression patterns of lncRNAs like TUG1 could

  20. Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

    Science.gov (United States)

    Pompas-Veganzones, N; Sandonis, V; Perez-Lanzac, Alberto; Beltran, M; Beardo, P; Juárez, A; Vazquez, F; Cozar, J M; Alvarez-Ossorio, J L; Sanchez-Carbayo, Marta

    2016-10-01

    Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed

  1. The inflammatory biomarker YKL-40 as a new prognostic marker for all-cause mortality in patients with heart failure

    DEFF Research Database (Denmark)

    Harutyunyan, Marina; Christiansen, Michael; Johansen, Julia S

    2011-01-01

    peptide (NT-proBNP) could be a new prognostic biomarker for all-cause mortality in patients with HF. METHODS AND RESULTS: A total of 717 of the 1000 patients with severe left ventricular systolic dysfunction included in the EchoCardiography and Heart Outcome Study were included in Denmark and had blood...... YKL-40 II to IV quartiles, respectively following multivariable adjustment for cardiovascular risk factors (age, left ventricular ejection fraction, gender, history of heart failure, ischemic heart disease, chronic pulmonary disease, diabetes mellitus, stroke, hypertension, NT-proBNP, hs......-CRP, and renal function). CONCLUSION: Serum YKL-40 is significantly associated with all-cause mortality in patients with HF and could potentially be a new prognostic biomarker in these patients....

  2. Multimarker Strategy for Heart Failure Prognostication. Value of Neurohormonal Biomarkers: Neprilysin vs NT-proBNP.

    Science.gov (United States)

    Bayes-Genis, Antoni; Barallat, Jaume; Galán, Amparo; de Antonio, Marta; Domingo, Mar; Zamora, Elisabet; Gastelurrutia, Paloma; Vila, Joan; Peñafiel, Judith; Gálvez-Montón, Carolina; Lupón, Josep

    2015-12-01

    prognosticator, while N-terminal pro-B-type natriuretic peptide lost significance as a risk stratifier in ambulatory patients with heart failure. Both biomarkers performed similarly in head-to-head analyses. Copyright © 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  3. Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology

    International Nuclear Information System (INIS)

    Bache, Michael; Bosco, Filippo G; Brøgger, Anna L; Frøhling, Kasper B; Boisen, Anja; Alstrøm, Tommy Sonne; Hwu, En-Te; Chen, Ching-Hsiu; Hwang, Ing-Shouh; Eugen-Olsen, Jesper

    2013-01-01

    In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels of soluble uPAR (suPAR) to infectious diseases, such as HIV, and certain types of cancer. Using hundreds of cantilevers and a DVD-based platform, cantilever deflection response from antibody–antigen recognition is investigated as a function of suPAR concentration. The goal is to provide a cheap and portable detection platform which can carry valuable prognostic information. In order to optimize the cantilever response the antibody immobilization and unspecific binding are initially characterized using quartz crystal microbalance technology. Also, the choice of antibody is explored in order to generate the largest surface stress on the cantilevers, thus increasing the signal. Using optimized experimental conditions the lowest detectable suPAR concentration is currently around 5 nM. The results reveal promising research strategies for the implementation of specific biochemical assays in a portable and high-throughput microsensor-based detection platform. (paper)

  4. Urinary long noncoding RNAs in nonmuscle-invasive bladder cancer: new architects in cancer prognostic biomarkers.

    Science.gov (United States)

    Terracciano, Daniela; Ferro, Matteo; Terreri, Sara; Lucarelli, Giuseppe; D'Elia, Carolina; Musi, Gennaro; de Cobelli, Ottavio; Mirone, Vincenzo; Cimmino, Amelia

    2017-06-01

    Several reports over the last 10 years provided evidence that long noncoding RNAs (lncRNAs) are often altered in bladder cancers. lncRNAs are longer than 200 nucleotides and function as important regulators of gene expression, interacting with the major pathways of cell growth, proliferation, differentiation, and survival. A large number of lncRNAs has oncogenic function and is more expressed in tumor compared with normal tissues. Their overexpression may be associated with tumor formation, progression, and metastasis in a variety of tumors including bladder cancer. Although lncRNAs have been shown to have critical regulatory roles in cancer biology, the biological functions and prognostic values in nonmuscle-invasive bladder cancer remain largely unknown. Nevertheless, a growing body of evidence suggests that several lncRNAs expression profiles in bladder malignancies are associated with poor prognosis, and they can be detected in biological fluids, such as urines. Here, we review current progress in the biology and the implication of lncRNAs associated with bladder cancer, and we discuss their potential use as diagnosis and prognosis biomarkers in bladder malignancies with a focus on their role in high-risk nonmuscle-invasive tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Prognostic stratification of acute pulmonary embolism: Focus on clinical aspects, imaging, and biomarkers

    Directory of Open Access Journals (Sweden)

    Luca Masotti

    2009-07-01

    Full Text Available Luca Masotti1, Marc Righini2, Nicolas Vuilleumier3, Fabio Antonelli4, Giancarlo Landini5, Roberto Cappelli6, Patrick Ray71Internal Medicine, 4Clinical Chemistry, Cecina Hospital, Cecina, Italy; 2Division of Angiology and Haemostasis, Department of Internal Medicine, Geneva University Hospital, Switzerland; 3Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals and University of Geneva, Switzerland; 5Internal Medicine, Santa Maria Nuova Hospital, Florence, Italy; 6Thrombosis Center, University of Siena, Siena, Italy; 7Department of Emergency Medicine, Centre Hospitalo-Universitaire Pitié-Salpêtrière, UPMC Paris 6, Paris, FranceAbstract: Pulmonary embolism (PE represents a common disease in emergency medicine and guidelines for diagnosis and treatment have had wide diffusion. However, PE morbidity and mortality remain high, especially when associated to hemodynamic instability or right ventricular dysfunction. Prognostic stratification to identify high risk patients needing to receive more aggressive pharmacological and closer monitoring is of utmost importance. Modern guidelines for management of acute PE are based on risk stratification using either clinical, radiological, or laboratory findings. This article reviews the modern treatment of acute PE, which is customized upon patient prognosis. Accordingly the current risk stratification tools described in the literature such as clinical scores, echocardiography, helical computer tomography, and biomarkers will be reviewed.Keywords: pulmonary embolism, prognosis, troponin, BNP, NT-proBNP, echocardiography, computer tomography

  6. The Role of Immunohistochemical Biomarkers as Prognostic Factors by the Use of a Tissue Microarray in Breast Cancer Patients Under 45-years-old

    International Nuclear Information System (INIS)

    Kim, Eun Seog; Choi, Doo Ho; Jin, So Young

    2008-01-01

    This study evaluates the association of estrogen receptor (ER), progesterone receptor (PR), Her-2, COX-2, and survivin with the clinicopathological features and outcomes in young Korean women with breast cancer using recently developed tissue microarray (TMA) technology. A cohort of 212 young patients with breast cancer diagnosed at the age of 45 years or younger from March 1994 to August 2005, were enrolled in this study. The age range of patients was 23∼45 years (median age, 39 years). The minimum and median follow-up periods were 24 months and 60 months, respectively. Serial sections of primary tumors were processed by the use of a TMA for immunohistochemical staining for five biomarkers. The correlation of these five biomarkers and the clinicopathological features and outcomes were analyzed by statistical methods. The majority of the patients were stage T1 (90 patients) or T2 (101 patients), and 105 patients (49.5%) had an axillary node metastasis. The 5-year overall and relapse free survival rates for all of the patients were 90.4% and 82.3%, respectively, and 36 patients had a locoregional or distant metastasis as a first event. Positive expression of ER, PR, Her-2, COX-2, and survivin was determined in 38.2%, 45.3%, 25.9%, 41.5%, and 43.4%, of the tumor samples, respectively. Tumor stage, nodal status, age, as well as expression of ER, PR, and HER-2 status were significantly associated with the disease free survival rate. Tumor stage, nodal status, as well as expression of ER, PR, and HER-2 were significantly related with the overall survival rate. Expression of COX-2 and survivin were not single independent prognostic factors for the disease free and overall survival rate although co-expression of HER-2 and COX-2 had a tendency as a poor prognostic factor. By multivariate analysis, only T stage and lymph node status were significant prognostic factors, and ER status was a marginally significant prognostic factor (p=0.075). Expression of ER, PR and HER-2

  7. Prognostic

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-10-01

    Conclusion: Our study suggests that lactate clearance could be used as a useful biomarker which is inexpensive and a reliable predictor of patient outcome in critically ill patients admitted to ICU with severe community-acquired pneumonia.

  8. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Directory of Open Access Journals (Sweden)

    Claudia Bühnemann

    Full Text Available Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases. Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%. The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36 was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality

  9. Quantification of the heterogeneity of prognostic cellular biomarkers in ewing sarcoma using automated image and random survival forest analysis.

    Science.gov (United States)

    Bühnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schäfer, Karl L; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C W; Athanasou, Nicholas A; Noble, J Alison; Hassan, A Bassim

    2014-01-01

    Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour

  10. Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

    Science.gov (United States)

    Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel

    2018-04-01

    The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid

  11. The prognostic blood biomarker proadrenomedullin for outcome prediction in patients with chronic obstructive pulmonary disease (COPD): a qualitative clinical review.

    Science.gov (United States)

    Schuetz, Philipp; Marlowe, Robert J; Mueller, Beat

    2015-03-01

    Plasma proadrenomedullin (ProADM) is a blood biomarker that may aid in multidimensional risk assessment of patients with chronic obstructive pulmonary disease (COPD). Co-secreted 1:1 with adrenomedullin (ADM), ProADM is a less biologically active, more chemically stable surrogate for this pluripotent regulatory peptide, which due to biological and ex vivo physical characteristics is difficult to reliably directly quantify. Upregulated by hypoxia, inflammatory cytokines, bacterial products, and shear stress and expressed widely in pulmonary cells and ubiquitously throughout the body, ADM exerts or mediates vasodilatory, natriuretic, diuretic, antioxidative, anti-inflammatory, antimicrobial, and metabolic effects. Observational data from four separate studies totaling 1366 patients suggest that as a single factor, ProADM is a significant independent, and accurate, long-term all-cause mortality predictor in COPD. This body of work also suggests that combined with different groups of demographic/clinical variables, ProADM provides significant incremental long-term mortality prediction power relative to the groups of variables alone. Additionally, the literature contains indications that ProADM may be a global cardiopulmonary stress marker, potentially supplying prognostic information when cardiopulmonary exercise testing results such as 6-min walk distance are unavailable due to time or other resource constraints or to a patient's advanced disease. Prospective, randomized, controlled interventional studies are needed to demonstrate whether ProADM use in risk-based guidance of site-of-care, monitoring, and treatment decisions improves clinical, quality-of-life, or pharmacoeconomic outcomes in patients with COPD.

  12. Usefulness and prognostic value of biomarkers in patients with community-acquired pneumonia in the emergency department.

    Science.gov (United States)

    Julián-Jiménez, Agustín; González Del Castillo, Juan; Candel, Francisco Javier

    2017-06-07

    Between all patients treated in the Emergency Department (ED), 1.35% are diagnosed with community-acquired pneumonia (CAP). CAP is the main cause of death due to infectious disease (10-14%) and the most frequent reason of sepsis-septic shock in the ED. In the last decade, the search for objective tools to help establishing an early diagnosis, bacterial aetiology, severity, suspicion of bacteremia and the prognosis of mortality has increased. Biomarkers have shown their usefulness in this matter. Procalcitonin (obtains the highest accuracy for CAP diagnosis, bacterial aetiology and the presence of bacteremia), lactate (biomarker of hypoxia and tissue hypoperfusion) and proadrenomedullin (which has the greatest accuracy to predict mortality which in combination with the prognostic severity scales obtains even better results). The aim of this review is to highlight recently published scientific evidence and to compare the utility and prognostic accuracy of the biomarkers in CAP patients treated in the ED. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  13. An Evaluation of Serum Procalcitonin and C-Reactive Protein Levels as Diagnostic and Prognostic Biomarkers of Severe Sepsis

    Directory of Open Access Journals (Sweden)

    Szederjesi Janos

    2015-10-01

    Full Text Available Background: Recommendations have been made, following the multicenter Surviving Sepsis Campaign study, to standardize the definition of severe sepsis with reference to several parameters such as haemodynamic stability, acid-base balance, bilirubin, creatinine, International Normalized Ratio (INR, urine output and pulmonary functional value of the ratio between arterial oxigen partial pressure and inspiratory oxigen concentration. Procalcitonin (PCT is considered to be a gold standard biomarker for the inflammatory response, and recent studies have shown that it may help to discover whether a seriously ill person is developing sepsis. C-reactive protein (CRP is also used as a marker of inflammation in the body, as its blood levels increase if there is any inflammation in the body. The aim of this study was to evaluate serum procalcitonin and C-reactive protein levels as diagnostic and prognostic biomarkers of severe sepsis.

  14. Statistical methods for the assessment of prognostic biomarkers(part II): calibration and re-classification

    NARCIS (Netherlands)

    Tripepi, Giovanni; Jager, Kitty J.; Dekker, Friedo W.; Zoccali, Carmine

    2010-01-01

    Calibration is the ability of a prognostic model to correctly estimate the probability of a given event across the whole range of prognostic estimates (for example, 30% probability of death, 40% probability of myocardial infarction, etc.). The key difference between calibration and discrimination is

  15. Cytogenetic prognostication within medulloblastoma subgroups.

    Science.gov (United States)

    Shih, David J H; Northcott, Paul A; Remke, Marc; Korshunov, Andrey; Ramaswamy, Vijay; Kool, Marcel; Luu, Betty; Yao, Yuan; Wang, Xin; Dubuc, Adrian M; Garzia, Livia; Peacock, John; Mack, Stephen C; Wu, Xiaochong; Rolider, Adi; Morrissy, A Sorana; Cavalli, Florence M G; Jones, David T W; Zitterbart, Karel; Faria, Claudia C; Schüller, Ulrich; Kren, Leos; Kumabe, Toshihiro; Tominaga, Teiji; Shin Ra, Young; Garami, Miklós; Hauser, Peter; Chan, Jennifer A; Robinson, Shenandoah; Bognár, László; Klekner, Almos; Saad, Ali G; Liau, Linda M; Albrecht, Steffen; Fontebasso, Adam; Cinalli, Giuseppe; De Antonellis, Pasqualino; Zollo, Massimo; Cooper, Michael K; Thompson, Reid C; Bailey, Simon; Lindsey, Janet C; Di Rocco, Concezio; Massimi, Luca; Michiels, Erna M C; Scherer, Stephen W; Phillips, Joanna J; Gupta, Nalin; Fan, Xing; Muraszko, Karin M; Vibhakar, Rajeev; Eberhart, Charles G; Fouladi, Maryam; Lach, Boleslaw; Jung, Shin; Wechsler-Reya, Robert J; Fèvre-Montange, Michelle; Jouvet, Anne; Jabado, Nada; Pollack, Ian F; Weiss, William A; Lee, Ji-Yeoun; Cho, Byung-Kyu; Kim, Seung-Ki; Wang, Kyu-Chang; Leonard, Jeffrey R; Rubin, Joshua B; de Torres, Carmen; Lavarino, Cinzia; Mora, Jaume; Cho, Yoon-Jae; Tabori, Uri; Olson, James M; Gajjar, Amar; Packer, Roger J; Rutkowski, Stefan; Pomeroy, Scott L; French, Pim J; Kloosterhof, Nanne K; Kros, Johan M; Van Meir, Erwin G; Clifford, Steven C; Bourdeaut, Franck; Delattre, Olivier; Doz, François F; Hawkins, Cynthia E; Malkin, David; Grajkowska, Wieslawa A; Perek-Polnik, Marta; Bouffet, Eric; Rutka, James T; Pfister, Stefan M; Taylor, Michael D

    2014-03-20

    Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials.

  16. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels.

    Science.gov (United States)

    El-Deeb, Wael M; Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI.

  17. Role of brain natriuretic peptide as a novel prognostic biomarker in acute ischemic stroke

    Directory of Open Access Journals (Sweden)

    Bindu Menon

    2016-01-01

    Full Text Available Aim: We investigated to study the prognostic importance of brain natriuretic peptide (BNP in ischemic stroke. Materials and Methods: We prospectively enrolled 100 patients with acute ischemic stroke and measured plasma BNP levels and compared with age- and sex-matched healthy controls. Risk factors, biochemical parameters, lipid profile, carotid and vertebral Doppler, imaging, and cardiac evaluation were done. Stroke severity was assessed by the National Institutes of Health Stroke Scale (NIHSS score on admission and functional disability by Barthel Index (BI at 3 months. Ischemic stroke subtype was classified according to the Oxfordshire Community Stroke Project (OCSP. Data were entered in MS Excel, and appropriate statistical analysis was done using the SPSS software version 21.0. A P = 0.05 was considered as significant. Results: Mean age of patients was 55.17 ± 11.37 years with a male:female ratio 3:1. OCSP showed total anterior circulation infarct (TACI 35, partial anterior circulation infarct 9, lacunar infarct 12, and posterior circulation infarct 44. NIHSS on admission was average 10 ± 7 and BI was 57 ± 30. BNP in patients (435 ng/ml was very high as compared to controls (<60 ng/ml (P < 0.001. There was a positive correlation between age and BNP (R2 = 0.34; P < 0.00; NIHSS and BNP (R2 = 0.255; P < 0.01, negative correlation between BI and BNP (R2 = −0.064; P < 0.01. Mean BNP levels across the OCSP showed higher values in TACI (F = 4.609 P = 0.005. Regression analysis showed that BNP can predict BI which was statistically significant. Conclusion: Plasma BNP levels was significantly elevated in patients with ischemic stroke. Our study concludes that high BNP levels are seen in large anterior circulation stroke and is a predictor for the poor functional outcome at 3 months. Determination of BNP levels as a biomarker could be helpful in predicting the outcome in stroke patients.

  18. A Systematic Review of the Diagnostic and Prognostic Value of Urinary Protein Biomarkers in Urothelial Bladder Cancer

    Science.gov (United States)

    D’Costa, Jamie J.; Goldsmith, James C.; Wilson, Jayne S.; Bryan, Richard T.; Ward, Douglas G.

    2016-01-01

    For over 80 years, cystoscopy has remained the gold-standard for detecting tumours of the urinary bladder. Since bladder tumours have a tendency to recur and progress, many patients are subjected to repeated cystoscopies during long-term surveillance, with the procedure being both unpleasant for the patient and expensive for healthcare providers. The identification and validation of bladder tumour specific molecular markers in urine could enable tumour detection and reduce reliance on cystoscopy, and numerous classes of biomarkers have been studied. Proteins represent the most intensively studied class of biomolecule in this setting. As an aid to researchers searching for better urinary biomarkers, we report a comprehensive systematic review of the literature and a searchable database of proteins that have been investigated to date. Our objective was to classify these proteins as: 1) those with robustly characterised sensitivity and specificity for bladder cancer detection; 2) those that show potential but further investigation is required; 3) those unlikely to warrant further investigation; and 4) those investigated as prognostic markers. This work should help to prioritise certain biomarkers for rigorous validation, whilst preventing wasted effort on proteins that have shown no association whatsoever with the disease, or only modest biomarker performance despite large-scale efforts at validation. PMID:27500198

  19. Prognostic significance of highly sulfated chondroitin sulfates in ovarian cancer defined by the single chain antibody GD3A11.

    Science.gov (United States)

    van der Steen, Sophieke C H A; van Tilborg, Angela A G; Vallen, Myrtille J E; Bulten, Johan; van Kuppevelt, Toin H; Massuger, Leon F A G

    2016-03-01

    The extracellular matrix (ECM) of ovarian cancer may provide a number of potential biomarkers. Chondroitin sulfate (CS), a class of sulfated polysaccharides, is abundantly present in the ECM of ovarian cancer. Structural alterations of CS chains (i.e. sulfation pattern) have been demonstrated to play a role in cancer development and progression. In this study we investigate the potential of highly sulfated CS as a biomarker in ovarian cancer using the single chain antibody GD3A11 selected by the phage display technology. The specificity of the antibody was determined by an indirect ELISA. GD3A11 epitope expression was assessed by immunohistochemistry in healthy organs, benign and malignant ovarian tumors (N=359) and correlated to clinical parameters. The CHST15 gene, responsible for the biosynthesis of highly sulfated CS was evaluated for mutation and methylation status. The GD3A11 epitope was minimally expressed in normal organs. Intense expression was observed in the ECM of different ovarian cancer subtypes, in contrast to benign ovarian tumors. Expression was independent of tumor grade, FIGO stage, and the use chemotherapy. For the aggressive ovarian cancer phenotype, intense expression was identified as an independent predictor for poor prognosis. CHST15 gene analysis showed no mutations nor an altered methylation status. Specific highly sulfated CS motifs expressed in the tumoral ECM hold biomarker potential in ovarian cancer patients. These matrix motifs constitute a novel class of biomarkers with prognostic significance and may be instrumental for innovative diagnostic and therapeutic applications (e.g. targeted therapy) in management of ovarian cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. pFAK-Y397 overexpression as both a prognostic and a predictive biomarker for patients with metastatic osteosarcoma.

    Science.gov (United States)

    Thanapprapasr, Kamolrat; Nartthanarung, Adisak; Thanapprapasr, Duangmani; Jinawath, Artit

    2017-01-01

    Focal adhesion kinase (FAK) is important for tumor cell survival and metastasis in various cancers. However, its expression and prognostic value in patients with metastatic osteosarcoma remain unknown. We investigated the expression of FAK and its phosphorylated form (pFAK-Y397) in osteosarcoma tissues from 53 patients by immunohistochemistry and evaluated their correlations with clinicopathologic characteristics and outcomes. The prognostic values were assessed using Kaplan-Meier survival and Cox regression analyses. Total FAK and pFAK-Y397 were overexpressed in 48 (90.6%) and 33 (62.3%) cases, respectively. pFAK-Y397 overexpression was correlated with poor histologic response after neoadjuvant chemotherapy in patients with osteosarcoma regardless of the presence of metastasis or not. Kaplan-Meier curve showed that patients with metastatic osteosarcoma with pFAK-Y397 overexpression had significantly worse overall survival (OS) than those with non-overexpression (P = 0.044). Multivariate Cox regression analysis confirmed pFAK-Y397 overexpression as an independent prognostic predictor for OS and post metastases OS (PMOS) (P = 0.017, P = 0.006, respectively). Age at diagnosis was also an independent indicator for PMOS (P = 0.003). However, total FAK expression was not correlated with any clinicopathologic characteristics or OS in patients with metastatic osteosarcoma. In conclusion, our findings identified FAK as a common aberrant protein overexpression in various subtypes of osteosarcoma. pFAK-Y397 overexpression can be used as a prognostic biomarker predicting poor OS for patients with metastatic osteosarcoma, and the expression of pFAK-Y397 differentiated good and poor responders to neoadjuvant chemotherapy.

  1. A Contemporary Review of the Treatment Landscape and the Role of Predictive and Prognostic Biomarkers in Pancreatic Adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Irene S. Yu

    2018-01-01

    Full Text Available Pancreatic cancer continues to represent one of the leading causes of cancer-related morbidity and mortality in the developed world. Over the past decade, novel systemic therapy combination regimens have contributed to clinically meaningful and statistically significant improvements in overall survival as compared to conventional monotherapy. However, the prognosis for most patients remains guarded secondary to the advanced stages of disease at presentation. There is growing consensus that outcomes can be further optimized with the use of predictive and prognostic biomarkers whereby the former can be enriching for patients who would benefit from therapies and the latter can inform decision-making regarding the need and timing of advanced care planning. One of the challenges of current biomarkers is the lack of standardization across clinical practices such that comparability between jurisdictions can be difficult or even impossible. This inconsistency can impede widespread implementation of their use. In this review article, we provide a comprehensive overview of the contemporary treatment options for pancreatic cancer and we offer some insights into the existing landscape and future directions of biomarker development for this disease.

  2. Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine

    DEFF Research Database (Denmark)

    Fredsøe, Jacob Christian; Rasmussen, Anne Karin; Thomsen, Anni Rønfeldt

    2017-01-01

    Background: Widespread use of prostate-specific antigen (PSA) testing for prostate cancer (PC) detection has led to extensive overdiagnosis and overtreatment. Urine-based microRNA (miRNA) biomarkers could be useful in PC diagnosis and prognosis. Objective: To train and validate urine-based micro......RNA (miRNA) biomarkers that may assist in PC diagnosis and prognosis. Design, setting, and participants: We profiled the expression levels of 92 miRNAs via reverse transcriptase–poymerase chain reaction in cell-free urine samples from 29 patients with benign prostatic hyperplasia (BPH) and 215 patients...... could help in primary diagnosis of PC and guide treatment decisions. Further validation studies are warranted. Patient summary: Using two large patient cohorts, we searched for novel prostate cancer biomarkers in urine. We found two new sets of microRNA biomarkers in urine that could accurately predict...

  3. Digital PCR analysis of circulating tumor DNA: a biomarker for chondrosarcoma diagnosis, prognostication, and residual disease detection.

    Science.gov (United States)

    Gutteridge, Alice; Rathbone, Victoria M; Gibbons, Rebecca; Bi, Mark; Archard, Nicholas; Davies, Kate E J; Brown, Jake; Plagnol, Vincent; Pillay, Nischalan; Amary, Fernanda; O'Donnell, Paul; Gupta, Manu; Tirabosco, Roberto; Flanagan, Adrienne M; Forshew, Tim

    2017-10-01

    Conventional chondrosarcoma is the most common primary bone tumor in adults. Prognosis corresponds with tumor grade but remains variable, especially for individuals with grade (G) II disease. There are currently no biomarkers available for monitoring or prognostication of chondrosarcoma. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for a broad range of tumor types. To date, little has been done to study the presence of ctDNA and its potential utility in the management of sarcomas, including chondrosarcoma. In this study, we have assessed ctDNA levels in a cohort of 71 patients, 32 with sarcoma, including 29 individuals with central chondrosarcoma (CS) and 39 with locally aggressive and benign bone and soft tissue tumors, using digital PCR. In patients with CS, ctDNA was detected in pretreatment samples in 14/29 patients, which showed clear correlation with tumor grade as demonstrated by the detection of ctDNA in all patients with GIII and dedifferentiated disease (n = 6) and in 8/17 patients with GII disease, but never associated with GI CS. Notably detection of ctDNA preoperatively in GII disease was associated with a poor outcome. A total of 14 patients with CS had ctDNA levels assessed at multiple time points and in most patients there was a clear reduction following surgical removal. This research lays the foundation for larger studies to assess the utility of ctDNA for chondrosarcoma diagnosis, prognostication, early detection of residual disease and monitoring disease progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Clinical significance of circulating miR-25-3p as a novel diagnostic and prognostic biomarker in osteosarcoma.

    Science.gov (United States)

    Fujiwara, Tomohiro; Uotani, Koji; Yoshida, Aki; Morita, Takuya; Nezu, Yutaka; Kobayashi, Eisuke; Yoshida, Akihiko; Uehara, Takenori; Omori, Toshinori; Sugiu, Kazuhisa; Komatsubara, Tadashi; Takeda, Ken; Kunisada, Toshiyuki; Kawamura, Machiko; Kawai, Akira; Ochiya, Takahiro; Ozaki, Toshifumi

    2017-05-16

    Emerging evidence has suggested that circulating microRNAs (miRNAs) in body fluids have novel diagnostic and prognostic significance for patients with malignant diseases. The lack of useful biomarkers is a crucial problem of bone and soft tissue sarcomas; therefore, we investigated the circulating miRNA signature and its clinical relevance in osteosarcoma. Global miRNA profiling was performed using patient serum collected from a discovery cohort of osteosarcoma patients and controls and cell culture media. The secretion of the detected miRNAs from osteosarcoma cells and clinical relevance of serum miRNA levels were evaluated using in vitro and in vivo models and a validation patient cohort. Discovery screening identified 236 serum miRNAs that were highly expressed in osteosarcoma patients compared with controls, and eight among these were also identified in the cell culture media. Upregulated expression levels of miR-17-5p and miR-25-3p were identified in osteosarcoma cells, and these were abundantly secreted into the culture media in tumor-derived exosomes. Serum miR-25-3p levels were significantly higher in osteosarcoma patients than in control individuals in the validation cohort, with favorable sensitivity and specificity compared with serum alkaline phosphatase. Furthermore, serum miR-25-3p levels at diagnosis were correlated with patient prognosis and reflected tumor burden in both in vivo models and patients; these associations were more sensitive than those of serum alkaline phosphatase. Serum-based circulating miR-25-3p may serve as a non-invasive blood-based biomarker for tumor monitoring and prognostic prediction in osteosarcoma patients.

  5. Prognostic power of biomarkers for short-term mortality in the elderly patients seen in Emergency Departments due to infections.

    Science.gov (United States)

    Julián-Jiménez, Agustín; Yañez, María Cecilia; González-Del Castillo, Juan; Salido-Mota, Manuel; Mora-Ordoñez, Begoña; Arranz-Nieto, María Jesús; Chanovas-Borras, Manuel R; Llopis-Roca, Ferrán; Mòdol-Deltell, Josep María; Muñoz, Gema

    2017-12-27

    To analyse and compare 30-day mortality prognostic power of several biomarkers (C-reactive protein, procalcitonin, lactate, suPAR and pro-adremomedullin) in elderly patients seen in Emergency Departments (ED) due to infections. Secondly, if these could improve the prognostic accuracy of sepsis criteria (systemic inflammatory response syndrome and quick Sepsis-related Organ Failure Assessment [qSOFA]). A prospective, observational, multicentre and analytical study. Patients aged 75 years and older who were treated for infection in the ED of 8 participating hospitals were enrolled consecutively. An assessment was made of 25 independent variables (epidemiological, comorbidity, functional, clinical and analytical variables) that could influence short-term mortality (at 30 days). The study included 136 patients, 13 (9.5%) of whom died within 30 days of visiting the ED. MR-proADM is the biomarker with the best area under the curve ROC to predict 30-day mortality (0.864; 95% CI 0.775-0.997; P2.07nmol/l, sensitivity of 77% and specificity of 96%. The qSOFA score≥2 had an area under the curve ROC of 0.763 (95% CI 0.623-0.903; P=.002), sensitivity of 76% and specificity of 75%. The mixed model (MR-proADM plus qSOFA≥2) improved the area under the curve ROC to 0.878 (95% CI 0.749-1; P2.07nmol/l) increased the predictive power of qSOFA. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  6. Radiomic Machine Learning Classifiers for Prognostic Biomarkers of Head & Neck Cancer

    Directory of Open Access Journals (Sweden)

    Chintan eParmar

    2015-12-01

    Full Text Available Introduction: Radiomics extracts and mines large number of medical imaging features in a non-invasive and cost-effective way. The underlying assumption of radiomics is that these imaging features quantify phenotypic characteristics of entire tumor. In order to enhance applicability of radiomics in clinical oncology, highly accurate and reliable machine learning approaches are required. In this radiomic study, thirteen feature selection methods and eleven machine learning classification methods were evaluated in terms of their performance and stability for predicting overall survival in head and neck cancer patients. Methods: Two independent head and neck cancer cohorts were investigated. Training cohort HN1 consisted 101 HNSCC patients. Cohort HN2 (n=95 was used for validation. A total of 440 radiomic features were extracted from the segmented tumor regions in CT images. Feature selection and classification methods were compared using an unbiased evaluation framework. Results: We observed that the three feature selection methods MRMR (AUC = 0.69, Stability = 0.66, MIFS (AUC = 0.66, Stability = 0.69, and CIFE (AUC = 0.68, Stability = 0.7 had high prognostic performance and stability. The three classifiers BY (AUC = 0.67, RSD = 11.28, RF (AUC = 0.61, RSD = 7.36, and NN (AUC = 0.62, RSD = 10.52 also showed high prognostic performance and stability. Analysis investigating performance variability indicated that the choice of classification method is the major factor driving the performance variation (29.02% of total variance. Conclusions: Our study identified prognostic and reliable machine learning methods for the prediction of overall survival of head and neck cancer patients. Identification of optimal machine-learning methods for radiomics based prognostic analyses could broaden the scope of radiomics in precision oncology and cancer care.

  7. Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.

    Science.gov (United States)

    Menéndez, R; Martínez, R; Reyes, S; Mensa, J; Filella, X; Marcos, M A; Martínez, A; Esquinas, C; Ramirez, P; Torres, A

    2009-07-01

    Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor alpha (TNFalpha) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, > or = 65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, > or = 65 years of age) scales. A total of 453 hospitalised CAP patients were included. The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.

  8. Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk.

    Science.gov (United States)

    Mahrooghy, Majid; Ashraf, Ahmed B; Daye, Dania; McDonald, Elizabeth S; Rosen, Mark; Mies, Carolyn; Feldman, Michael; Kontos, Despina

    2015-06-01

    Heterogeneity in cancer can affect response to therapy and patient prognosis. Histologic measures have classically been used to measure heterogeneity, although a reliable noninvasive measurement is needed both to establish baseline risk of recurrence and monitor response to treatment. Here, we propose using spatiotemporal wavelet kinetic features from dynamic contrast-enhanced magnetic resonance imaging to quantify intratumor heterogeneity in breast cancer. Tumor pixels are first partitioned into homogeneous subregions using pharmacokinetic measures. Heterogeneity wavelet kinetic (HetWave) features are then extracted from these partitions to obtain spatiotemporal patterns of the wavelet coefficients and the contrast agent uptake. The HetWave features are evaluated in terms of their prognostic value using a logistic regression classifier with genetic algorithm wrapper-based feature selection to classify breast cancer recurrence risk as determined by a validated gene expression assay. Receiver operating characteristic analysis and area under the curve (AUC) are computed to assess classifier performance using leave-one-out cross validation. The HetWave features outperform other commonly used features (AUC = 0.88 HetWave versus 0.70 standard features). The combination of HetWave and standard features further increases classifier performance (AUCs 0.94). The rate of the spatial frequency pattern over the pharmacokinetic partitions can provide valuable prognostic information. HetWave could be a powerful feature extraction approach for characterizing tumor heterogeneity, providing valuable prognostic information.

  9. Nanomechanical recognition of prognostic biomarker suPAR with DVD-ROM optical technology

    DEFF Research Database (Denmark)

    Bache, Michael; Bosco, Filippo; Brøgger, Anna Line

    2013-01-01

    In this work the use of a high-throughput nanomechanical detection system based on a DVD-ROM optical drive and cantilever sensors is presented for the detection of urokinase plasminogen activator receptor inflammatory biomarker (uPAR). Several large scale studies have linked elevated levels...

  10. New prognostic factor telomerase reverse transcriptase promotor mutation presents without MR imaging biomarkers in primary glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Ersoy, Tunc F.; Simon, Matthias [University Hospital Bonn, Department of Neurosurgery and Stereotaxy, Bonn (Germany); Ev. Krankenhaus Bielefeld, Department of Neurosurgery, Bielefeld (Germany); Keil, Vera C.; Hadizadeh, Dariusch R.; Schild, Hans H. [University Hospital Bonn, Department of Radiology, Bonn (Germany); Gielen, Gerrit H.; Waha, Andreas [University Hospital Bonn, Institute of Neuropathology, Bonn (Germany); Fimmers, Rolf [IMBIE, University Hospital Bonn, Bonn (Germany); Heidenreich, Barbara; Kumar, Rajiv [DFKZ, Department of Molecular Genetic Epidemiology, Heidelberg (Germany)

    2017-12-15

    Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status. Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) (https: //wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project) imaging criteria by three radiological raters. TERT mutation and O{sup 6}-methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression. No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0-19.0) vs. 24.0 (16.6-37.5) all cm{sup 3}; p = 0.007] and prolonged median overall survival [17.0 (11.5-28.0) vs. 9.0 (4.0-12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01). Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas. (orig.)

  11. [Diagnostic and prognostic power of biomarkers to improve the management of community acquired pneumonia in the emergency department].

    Science.gov (United States)

    Julián-Jiménez, Agustín; Timón Zapata, Jesús; Laserna Mendieta, Emilio José; Sicilia-Bravo, Isabel; Palomo-de Los Reyes, María José; Cabezas-Martínez, Angeles; Laín-Terés, Natividad; Estebaran-Martín, Josefa; Lozano-Ancín, Agustín; Cuena-Boy, Rafael

    2014-04-01

    To analyse the usefulness and performance of several biomarkers [C-reactive protein (CRP), mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT)] and lactate in predicting short- and medium-term mortality compared with the prognostic severity scales (PSS) usually employed for community-acquired pneumonia (CAP) and in assessing the aetiological suspicion of infection by Streptococcus pneumoniae and bacteraemia. Observational, prospective and analytical study was conducted on patients who were diagnosed with CAP in our emergency department (ED). The data collected included socio-demographic and comorbidity variables, Charlson index, priority level according to the Spanish Triage System (STS), stage in the Pneumonia Severity Index (PSI) and in the CURB-65 (confusion, urea, respiratory rate, blood pressure and age ≥65years), criteria of severe CAP, microbiological studies, and biomarkers determinations. The patients were followed-up for 180days to calculate the prognostic power and the diagnostic performance for bacteraemia and aetiology. A total of 127patients were finally enrolled in the study. The 30-day mortality was 10.3% (13), and 22.6% (28) at 180 days. Blood cultures were positive in 29 patients (23%) and S.pneumoniae was identified as the responsible pathogen in 28 cases (22.2%). The area under the ROC curve (AUC-ROC) for lactate and MR-proADM to predict 30-day mortality was 0.898 (95%CI: 0.824-0.973; P0.85ng/ml, the NPV and the LR+ were 96.6% and 5.89%, respectively, to predict a S.pneumoniae infection. MR-proADM and lactate showed a similar or even better performance for 30-day intra-hospital mortality than PSI, CURB-65, STS and CAP severity criteria in patients diagnosed with CAP (P>.05). Furthermore, the MR-proADM capacity to predict 180-day mortality was higher than PSS and the rest of biomarkers (P>.05), and its AUC-ROC increased if it was used in combination with PSI, CURB65 and STS. The determination of PCT has a remarkable diagnostic

  12. Plasma levels of the MMP-9:TIMP-1 complex as prognostic biomarker in breast cancer: a retrospective study

    International Nuclear Information System (INIS)

    Thorsen, Stine B; Møller, Susanne; Brünner, Nils; Schrohl, Anne-Sofie; Stenvang, Jan; Christensen, Sarah LT; Würtz, Sidse Ø; Lundberg, Martin; Nielsen, Birgitte S; Vinther, Lena; Knowles, Mick; Gee, Nick; Fredriksson, Simon

    2013-01-01

    Worldwide more than one million women are annually diagnosed with breast cancer. A considerable fraction of these women receive systemic adjuvant therapy; however, some are cured by primary surgery and radiotherapy alone. Prognostic biomarkers guide stratification of patients into different risk groups and hence improve management of breast cancer patients. Plasma levels of Matrix Metalloproteinase-9 (MMP-9) and its natural inhibitor Tissue inhibitor of metalloproteinase-1 (TIMP-1) have previously been associated with poor patient outcome and resistance to certain forms of chemotherapy. To pursue additional prognostic information from MMP-9 and TIMP-1, the level of the MMP-9 and TIMP-1 complex (MMP-9:TIMP-1) was investigated in plasma from breast cancer patients. Detection of protein:protein complexes in plasma was performed using a commercially available ELISA kit and, for the first time, the highly sensitive in-solution proximity ligation assay (PLA). We screened plasma from 465 patients with primary breast cancer for prognostic value of the MMP-9:TIMP-1 complex. Both assays were validated and applied for quantification of MMP-9:TIMP-1 concentration. In this retrospective study, we analyzed the association between the concentration of the MMP-9:TIMP-1 complex and clinicopathological data and disease free survival (DFS) in univariate and multivariate survival analyses. Following successful validation both assays were applied for MMP-9:TIMP-1 measurements. Of the clinicopathological parameters, only menopausal status demonstrated significant association with the MMP-9:TIMP-1 complex; P = 0.03 and P = 0.028 for the ELISA and PLA measurements, respectively. We found no correlation between the MMP-9:TIMP-1 protein complex and DFS neither in univariate nor in multivariate survival analyses. Despite earlier reports linking MMP-9 and TIMP-1 with prognosis in breast cancer patients, we here demonstrate that plasma levels of the MMP-9:TIMP-1 protein complex hold no

  13. Gene profiling and circulating tumor cells as biomarker to prognostic of patients with locoregional breast cancer.

    Science.gov (United States)

    Kuniyoshi, Renata K; Gehrke, Flávia de Sousa; Alves, Beatriz C A; Vilas-Bôas, Viviane; Coló, Anna E; Sousa, Naiara; Nunes, João; Fonseca, Fernando L A; Del Giglio, Auro

    2015-09-01

    The gene profile of primary tumors, as well as the identification of circulating tumor cells (CTCs), can provide important prognostic and predictive information. In this study, our objective was to perform tumor gene profiling (TGP) in combination with CTC characterization in women with nonmetastatic breast cancer. Biological samples (from peripheral blood and tumors) from 167 patients diagnosed with stage I, II, and III mammary carcinoma, who were also referred for adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters: (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the expression of 21 genes in paraffin-embedded tissue samples by quantitative multiplex RT-PCR with the Plexor® system. We observed a statistically significant correlation between the progression-free interval (PFI) and the clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of hormone receptors in the tumor (p = 0.0432). We observed no correlation between the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC fraction prior to the start of treatment or in the two following readouts. Multivariate analysis revealed that only the TGP score significantly correlated with the PFI (p = 0.029247). The TGP is an important prognostic variable for patients with locoregional breast cancer. The presence of CTCs adds no prognostic value to the information already provided by the TGP.

  14. The NHLBI LAM Registry: Prognostic physiological and radiological biomarkers emerge from a 15-year prospective longitudinal analysis.

    Science.gov (United States)

    Gupta, Nishant; Lee, Hye-Seung; Ryu, Jay H; Taveira-DaSilva, Angelo M; Beck, Gerald J; Lee, Jar-Chi; McCarthy, Kevin; Finlay, Geraldine A; Brown, Kevin K; Ruoss, Stephen J; Avila, Nilo A; Moss, Joel; McCormack, Francis X

    2018-06-22

    The natural history of lymphangioleiomyomatosis is mainly derived from retrospective cohort analyses and remains incompletely understood. A National Institutes of Health LAM Registry was established to define the natural history and identify prognostic biomarkers that can help guide management and decision-making in patients with LAM. A linear mixed effects model was employed to compute the rate of decline of FEV1, and identify variables impacting FEV1 decline among 217 registry patients who enrolled from 1998-2001. Prognostic variables associated with progression to death/lung transplantation were identified using a Cox proportional hazard model. Mean annual decline of FEV1 was 89±53 ml/year, and remained remarkably constant regardless of baseline lung function. FEV1 decline was more rapid in those with greater cyst profusion on CT scan (p=0.02), and in premenopausal subjects (118ml/year) compared to postmenopausal subjects (74ml/year), (p=0.003). There were 26 deaths and 43 lung transplants during the evaluation period. Estimated 5-, 10-, 15-, and 20-year transplant-free survival rates were 95%, 85%, 75%, and 64%, respectively. Postmenopausal status (hazard ratio 0.30, p=0.0002) and higher baseline FEV1 (hazard ratio 0.97, p=0.008) or DLCO (hazard ratio 0.97, p=0.001) were independently associated with a lower risk of progression to death or lung transplantation. The median transplant-free survival in patients with LAM is greater than 20 years. Menopausal status as well as structural and physiological markers of disease severity significantly affect the rate of decline of FEV1 and progression to death or lung transplantation in LAM. Copyright © 2018. Published by Elsevier Inc.

  15. Potentials of single-cell biology in identification and validation of disease biomarkers.

    Science.gov (United States)

    Niu, Furong; Wang, Diane C; Lu, Jiapei; Wu, Wei; Wang, Xiangdong

    2016-09-01

    Single-cell biology is considered a new approach to identify and validate disease-specific biomarkers. However, the concern raised by clinicians is how to apply single-cell measurements for clinical practice, translate the message of single-cell systems biology into clinical phenotype or explain alterations of single-cell gene sequencing and function in patient response to therapies. This study is to address the importance and necessity of single-cell gene sequencing in the identification and development of disease-specific biomarkers, the definition and significance of single-cell biology and single-cell systems biology in the understanding of single-cell full picture, the development and establishment of whole-cell models in the validation of targeted biological function and the figure and meaning of single-molecule imaging in single cell to trace intra-single-cell molecule expression, signal, interaction and location. We headline the important role of single-cell biology in the discovery and development of disease-specific biomarkers with a special emphasis on understanding single-cell biological functions, e.g. mechanical phenotypes, single-cell biology, heterogeneity and organization of genome function. We have reason to believe that such multi-dimensional, multi-layer, multi-crossing and stereoscopic single-cell biology definitely benefits the discovery and development of disease-specific biomarkers. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  16. Long non-coding RNA TUG1 as a potential prognostic biomarker in human cancers: a meta-analysis.

    Science.gov (United States)

    Ma, Peng-Ju; Guan, Qing-Kai; Meng, Lei; Qin, Nan; Zhao, Jia; Jin, Bao-Zhe

    2017-09-22

    LncRNA taurine upregulated gene 1 (TUG1) is reportedly dysregulated in various cancers. We performed this meta-analysis to clarify the usefulness of TUG1 as a prognostic marker in malignant tumors. The PubMed, Medline, OVID, Cochrane Library, and Web of Science databases were searched from inception to Jan 11, 2017. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to explore the relationship between TUG1 expression and overall survival (OS). Odds ratios (ORs) were calculated to assess the association between TUG1 expression and pathological parameters. Thirteen original studies covering 1,274 cancer patients were included in this meta-analysis. The pooled HR suggested that high TUG1 expression correlated with poor OS (pooled HR=1.41, 95% CI: 1.01-1.98) in cancer types other than non-small cell lung cancer. TUG1 expression was also related to distant metastasis (OR=3.24, 95% CI: 1.18-8.93), large tumor size (OR=4.07, 95% CI: 1.08-15.28) and advanced tumor stage (OR=3.45, 95% CI: 2.19-5.44). Begg's funnel plot and Egger's test showed no evidence of obvious asymmetry for overall survival or tumor stage. Thus high TUG1 expression appears predictive of poor OS, distant metastasis, advanced tumor stage and large tumor size. This suggests TUG1 expression could serve as a biomarker for poor prognosis in cancers.

  17. Polymorphisms within the APOBR gene are highly associated with milk levels of prognostic ketosis biomarkers in dairy cows.

    Science.gov (United States)

    Tetens, Jens; Heuer, Claas; Heyer, Iris; Klein, Matthias S; Gronwald, Wolfram; Junge, Wolfgang; Oefner, Peter J; Thaller, Georg; Krattenmacher, Nina

    2015-04-01

    Essentially all high-yielding dairy cows experience a negative energy balance during early lactation leading to increased lipomobilization, which is a normal physiological response. However, a severe energy deficit may lead to high levels of ketone bodies and, subsequently, to subclinical or clinical ketosis. It has previously been reported that the ratio of glycerophosphocholine to phosphocholine in milk is a prognostic biomarker for the risk of ketosis in dairy cattle. It was hypothesized that this ratio reflects the ability to break down blood phosphatidylcholine as a fatty acid resource. In the current study, 248 animals from a previous study were genotyped with Illumina BovineSNP50 BeadChip, and genome-wide association studies were carried out for the milk levels of phosphocholine, glycerophosphocholine, and the ratio of both metabolites. It was demonstrated that the latter two traits are heritable with h2 = 0.43 and h2 = 0.34, respectively. A major quantitative trait locus was identified on cattle chromosome 25. The APOBR gene, coding for the apolipoprotein B receptor, is located within this region and was analyzed as a candidate gene. The analysis revealed highly significant associations of polymorphisms within the gene with glycerophosphocholine as well as the metabolite ratio. These findings support the hypothesis that differences in the ability to take up blood phosphatidylcholine from low-density lipoproteins play an important role in early lactation metabolic stability of dairy cows and indicate APOBR to contain a causative variant. Copyright © 2015 the American Physiological Society.

  18. Potential of DNA methylation in rectal cancer as diagnostic and prognostic biomarkers

    Science.gov (United States)

    Exner, Ruth; Pulverer, Walter; Diem, Martina; Spaller, Lisa; Woltering, Laura; Schreiber, Martin; Wolf, Brigitte; Sonntagbauer, Markus; Schröder, Fabian; Stift, Judith; Wrba, Fritz; Bergmann, Michael; Weinhäusel, Andreas; Egger, Gerda

    2015-01-01

    Background: Aberrant DNA methylation is more prominent in proximal compared with distal colorectal cancers. Although a number of methylation markers were identified for colon cancer, yet few are available for rectal cancer. Methods: DNA methylation differences were assessed by a targeted DNA microarray for 360 marker candidates between 22 fresh frozen rectal tumour samples and 8 controls and validated by microfluidic high-throughput and methylation-sensitive qPCR in fresh frozen and formalin-fixed paraffin-embedded (FFPE) samples, respectively. The CpG island methylator phenotype (CIMP) was assessed by MethyLight in FFPE material from 78 patients with pT2 and pT3 rectal adenocarcinoma. Results: We identified and confirmed two novel three-gene signatures in fresh frozen samples that can distinguish tumours from adjacent tissue as well as from blood with a high sensitivity and specificity of up to 1 and an AUC of 1. In addition, methylation of individual CIMP markers was associated with specific clinical parameters such as tumour stage, therapy or patients' age. Methylation of CDKN2A was a negative prognostic factor for overall survival of patients. Conclusions: The newly defined methylation markers will be suitable for early disease detection and monitoring of rectal cancer. PMID:26335606

  19. Gastric cancer: texture analysis from multidetector computed tomography as a potential preoperative prognostic biomarker

    Energy Technology Data Exchange (ETDEWEB)

    Giganti, Francesco; Salerno, Annalaura; Marra, Paolo; Esposito, Antonio; Del Maschio, Alessandro; De Cobelli, Francesco [Department of Radiology and Centre for Experimental Imaging San Raffaele Scientific Institute, Milan (Italy); San Raffaele Vita-Salute University, Milan (Italy); Antunes, Sofia [San Raffaele Scientific Institute, Centre for Experimental Imaging, Milan (Italy); Ambrosi, Alessandro [San Raffaele Vita-Salute University, Milan (Italy); Nicoletti, Roberto [Department of Radiology and Centre for Experimental Imaging San Raffaele Scientific Institute, Milan (Italy); Orsenigo, Elena [San Raffaele Scientific Institute, Department of Surgery, Milan (Italy); Chiari, Damiano; Staudacher, Carlo [San Raffaele Vita-Salute University, Milan (Italy); San Raffaele Scientific Institute, Department of Surgery, Milan (Italy); Albarello, Luca [San Raffaele Scientific Institute, Pathology Unit, Milan (Italy)

    2017-05-15

    To investigate the association between preoperative texture analysis from multidetector computed tomography (MDCT) and overall survival in patients with gastric cancer. Institutional review board approval and informed consent were obtained. Fifty-six patients with biopsy-proved gastric cancer were examined by MDCT and treated with surgery. Image features from texture analysis were quantified, with and without filters for fine to coarse textures. The association with survival time was assessed using Kaplan-Meier and Cox analysis. The following parameters were significantly associated with a negative prognosis, according to different thresholds: energy [no filter] - Logarithm of relative risk (Log RR): 3.25; p = 0.046; entropy [no filter] (Log RR: 5.96; p = 0.002); entropy [filter 1.5] (Log RR: 3.54; p = 0.027); maximum Hounsfield unit value [filter 1.5] (Log RR: 3.44; p = 0.027); skewness [filter 2] (Log RR: 5.83; p = 0.004); root mean square [filter 1] (Log RR: - 2.66; p = 0.024) and mean absolute deviation [filter 2] (Log RR: - 4.22; p = 0.007). Texture analysis could increase the performance of a multivariate prognostic model for risk stratification in gastric cancer. Further evaluations are warranted to clarify the clinical role of texture analysis from MDCT. (orig.)

  20. Elevated Adenylyl Cyclase 9 Expression Is a Potential Prognostic Biomarker for Patients with Colon Cancer.

    Science.gov (United States)

    Yi, Hua; Wang, Kun; Jin, Jun-Feng; Jin, He; Yang, Lihua; Zou, Yidan; Du, Biaoyan; Liu, Xiaodong

    2018-01-02

    BACKGROUND Adenylyl cyclase 9 (ADCY9) is an enzyme that modulates signal transduction by producing the second messenger, cyclic adenosine monophosphate (cAMP). The aim of the present study was to investigate the association of ADCY9 expression with clinicopathological features and disease-free survival of colon cancer patients. MATERIAL AND METHODS Immunohistochemistry staining with ADCY9 antibody was performed on a tissue microarray. Immunoreactivity scores (IRS) were recorded and applied for association analysis. ADCY9 mRNA expression and clinicopathogical information were also extracted from TCGA colon cancer dataset and analyzed using univariate and multivariate Cox proportional hazards models.  RESULTS ADCY9 IRS was significantly higher (P=0.002) in tumor tissues (6.40±1.26, n=200) than in adjacent normal samples (4.13±0.83, n=8). The IRS and mRNA expression of ADCY9 were correlated to colon cancer TNM staging. Longer disease-free survival was observed in patients with lower ADCY9 expression (P=0.001). In the multivariate models, ADCY9 expression level (hazard ratio [HR] 5.495, 95% confidence interval [CI] 1.753-17.227, P=0.003), and distant metastasis (HR 4.329, 95% CI 1.374-13.636, P=0.012) were still associated with disease-free survival. CONCLUSIONS High ADCY9 expression is a poor prognostic factor for disease-free survival in colon cancer.

  1. Mucins as diagnostic and prognostic biomarkers in a fish-parasite model: transcriptional and functional analysis.

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    Jaume Pérez-Sánchez

    Full Text Available Mucins are O-glycosylated glycoproteins present on the apex of all wet-surfaced epithelia with a well-defined expression pattern, which is disrupted in response to a wide range of injuries or challenges. The aim of this study was to identify mucin gene sequences of gilthead sea bream (GSB, to determine its pattern of distribution in fish tissues and to analyse their transcriptional regulation by dietary and pathogenic factors. Exhaustive search of fish mucins was done in GSB after de novo assembly of next-generation sequencing data hosted in the IATS transcriptome database (www.nutrigroup-iats.org/seabreamdb. Six sequences, three categorized as putative membrane-bound mucins and three putative secreted-gel forming mucins, were identified. The transcriptional tissue screening revealed that Muc18 was the predominant mucin in skin, gills and stomach of GSB. In contrast, Muc19 was mostly found in the oesophagus and Muc13 was along the entire intestinal tract, although the posterior intestine exhibited a differential pattern with a high expression of an isoform that does not share a clear orthologous in mammals. This mucin was annotated as intestinal mucin (I-Muc. Its RNA expression was highly regulated by the nutritional background, whereas the other mucins, including Muc2 and Muc2-like, were expressed more constitutively and did not respond to high replacement of fish oil (FO by vegetable oils (VO in plant protein-based diets. After challenge with the intestinal parasite Enteromyxum leei, the expression of a number of mucins was decreased mainly in the posterior intestine of infected fish. But, interestingly, the highest down-regulation was observed for the I-Muc. Overall, the magnitude of the changes reflected the intensity and progression of the infection, making mucins and I-Muc, in particular, reliable markers of prognostic and diagnostic value of fish intestinal health.

  2. Preoperative Serum Thymidine Kinase Activity as Novel Monitoring, Prognostic, and Predictive Biomarker in Pancreatic Cancer.

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    Felix, Klaus; Hinz, Ulf; Dobiasch, Sophie; Hackert, Thilo; Bergmann, Frank; Neumüller, Magnus; Gronowitz, Simon; Bergqvist, Mattias; Strobel, Oliver

    2018-01-01

    The aim of the study was to investigate serum thymidine kinase 1 (S-TK) activity as a diagnostic and prognostic marker for patients with pancreatic ductal adenocarcinoma (PDAC). Using the sensitive TK activity assay DiviTum, preoperative serum samples from 404 PDAC, 28 chronic pancreatitis, and 25 autoimmune pancreatitis patients and 83 healthy volunteers were analyzed. The preoperative S-TK activities of 54 PDAC patients who received neoadjuvant therapy (nTx) were also compared with those of 258 PDAC patients who did not receive nTx. The preoperative S-TK activities of PDAC patients were significantly higher and discriminatory from autoimmune and chronic pancreatitis patients and control groups. The S-TK activity in PDAC patients was associated with overall survival. Patients with S-TK activity of less than 80 Du (DiviTum units)/L demonstrated median survival of 20.3 months with an estimated 18.0% 5-year survival rate; for S-TK activity of 80 Du/L or greater, median survival was 15.1 months with a 6.8% 5-year survival rate. For early-stage PDAC, these differences were even more pronounced. The S-TK activity in the nTx group was significantly higher than that in the group not receiving nTx. Pancreatic ductal adenocarcinomas reveal a significant increase in S-TK activity, which is associated with overall survival, especially in early tumor stages. Serum thymidine kinase 1 activity may be a useful parameter for monitoring nTx efficacy.

  3. Identification and Validation of PCAT14 as Prognostic Biomarker in Prostate Cancer

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    Sudhanshu Shukla

    2016-08-01

    Full Text Available Rapid advances in the discovery of long noncoding RNAs (lncRNAs have identified lineage- and cancer-specific biomarkers that may be relevant in the clinical management of prostate cancer (PCa. Here we assembled and analyzed a large RNA-seq dataset, from 585 patient samples, including benign prostate tissue and both localized and metastatic PCa to discover and validate differentially expressed genes associated with disease aggressiveness. We performed Sample Set Enrichment Analysis (SSEA and identified genes associated with low versus high Gleason score in the RNA-seq database. Comparing Gleason 6 versus 9+ PCa samples, we identified 99 differentially expressed genes with variable association to Gleason grade as well as robust expression in prostate cancer. The top-ranked novel lncRNA PCAT14, exhibits both cancer and lineage specificity. On multivariate analysis, low PCAT14 expression independently predicts for BPFS (P = .00126, PSS (P = .0385, and MFS (P = .000609, with trends for OS as well (P = .056. An RNA in-situ hybridization (ISH assay for PCAT14 distinguished benign vs malignant cases, as well as high vs low Gleason disease. PCAT14 is transcriptionally regulated by AR, and endogenous PCAT14 overexpression suppresses cell invasion. Thus, Using RNA-sequencing data we identify PCAT14, a novel prostate cancer and lineage-specific lncRNA. PCAT14 is highly expressed in low grade disease and loss of PCAT14 predicts for disease aggressiveness and recurrence.

  4. GC-MS based Gestational Diabetes Mellitus longitudinal study: Identification of 2-and 3-hydroxybutyrate as potential prognostic biomarkers.

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    Dudzik, Danuta; Zorawski, Marcin; Skotnicki, Mariusz; Zarzycki, Wieslaw; García, Antonia; Angulo, Santiago; Lorenzo, M Paz; Barbas, Coral; Ramos, M Pilar

    2017-09-10

    Gestational Diabetes Mellitus (GDM) causes severe short- and long-term complications for the mother, fetus and neonate, including type 2-diabetes (T2DM) later in life. In this pilot study, GC-Q/MS analysis was applied for plasma metabolomics fingerprinting of 24 healthy and 24 women with GDM at different stages of gestation (second and third trimester) and postpartum (one and three months). Multivariate (unsupervised and supervised) statistical analysis was performed to investigate variance in the data, identify outliers and for unbiased assessment of data quality. Plasma fingerprints allowed for the discrimination of GDM pregnant women from controls both in the 2nd and 3rd trimesters of gestation. However, metabolic profiles tended to be similar after delivery. Follow up of these women revealed that 4 of them developed T2DM within 2 years postpartum. Multivariate PLS-DA models limited to women with GDM showed clear separation 3 months postpartum. In the 2nd trimester of gestation there was also a clear separation between GDM women that were normoglycemic after pregnancy and those with recognized postpartum T2DM. Metabolites that had the strongest discriminative power between these groups in the 2nd trimester of gestation were 2-hydroxybutyrate, 3-hydroxybutyrate, and stearic acid. We have described, that early GDM comprises metabotypes that are associated with the risk of future complications, including postpartum T2DM. In this pilot study, we provide evidence that 2-hydroxybutyrate and 3-hydroxybutyrate may be considered as future prognostic biomarkers to predict the onset of diabetic complications in women with gestational diabetes after delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Single-gene prognostic signatures for advanced stage serous ovarian cancer based on 1257 patient samples.

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    Zhang, Fan; Yang, Kai; Deng, Kui; Zhang, Yuanyuan; Zhao, Weiwei; Xu, Huan; Rong, Zhiwei; Li, Kang

    2018-04-16

    We sought to identify stable single-gene prognostic signatures based on a large collection of advanced stage serous ovarian cancer (AS-OvCa) gene expression data and explore their functions. The empirical Bayes (EB) method was used to remove the batch effect and integrate 8 ovarian cancer datasets. Univariate Cox regression was used to evaluate the association between gene and overall survival (OS). The Database for Annotation, Visualization and Integrated Discovery (DAVID) tool was used for the functional annotation of genes for Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The batch effect was removed by the EB method, and 1257 patient samples were used for further analysis. We selected 341 single-gene prognostic signatures with FDR matrix organization, focal adhesion and DNA replication which are closely associated with cancer. We used the EB method to remove the batch effect of 8 datasets, integrated these datasets and identified stable prognosis signatures for AS-OvCa.

  6. Radiogenomics of hepatocellular carcinoma: multiregion analysis-based identification of prognostic imaging biomarkers by integrating gene data—a preliminary study

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    Xia, Wei; Chen, Ying; Zhang, Rui; Yan, Zhuangzhi; Zhou, Xiaobo; Zhang, Bo; Gao, Xin

    2018-02-01

    Our objective was to identify prognostic imaging biomarkers for hepatocellular carcinoma in contrast-enhanced computed tomography (CECT) with biological interpretations by associating imaging features and gene modules. We retrospectively analyzed 371 patients who had gene expression profiles. For the 38 patients with CECT imaging data, automatic intra-tumor partitioning was performed, resulting in three spatially distinct subregions. We extracted a total of 37 quantitative imaging features describing intensity, geometry, and texture from each subregion. Imaging features were selected after robustness and redundancy analysis. Gene modules acquired from clustering were chosen for their prognostic significance. By constructing an association map between imaging features and gene modules with Spearman rank correlations, the imaging features that significantly correlated with gene modules were obtained. These features were evaluated with Cox’s proportional hazard models and Kaplan-Meier estimates to determine their prognostic capabilities for overall survival (OS). Eight imaging features were significantly correlated with prognostic gene modules, and two of them were associated with OS. Among these, the geometry feature volume fraction of the subregion, which was significantly correlated with all prognostic gene modules representing cancer-related interpretation, was predictive of OS (Cox p  =  0.022, hazard ratio  =  0.24). The texture feature cluster prominence in the subregion, which was correlated with the prognostic gene module representing lipid metabolism and complement activation, also had the ability to predict OS (Cox p  =  0.021, hazard ratio  =  0.17). Imaging features depicting the volume fraction and textural heterogeneity in subregions have the potential to be predictors of OS with interpretable biological meaning.

  7. Prognostic implications of atrial fibrillation in patients undergoing myocardial perfusion single-photon emission computed tomography.

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    Abidov, Aiden; Hachamovitch, Rory; Rozanski, Alan; Hayes, Sean W; Santos, Marcia M; Sciammarella, Maria G; Cohen, Ishac; Gerlach, James; Friedman, John D; Germano, Guido; Berman, Daniel S

    2004-09-01

    The aim of this research was to determine whether presence of atrial fibrillation (AF) provides incremental prognostic information relative to myocardial perfusion single-photon emission computed tomography (MPS) with respect to risk of cardiac death (CD). The prognostic significance of AF in patients undergoing MPS is not known. A total of 16,048 consecutive patients undergoing MPS were followed-up for a mean of 2.21 +/- 1.15 years for the development of CD. Of those, 384 patients (2.4%) had AF. Cox proportional hazards method was used to compare clinical and perfusion data for the prediction of CD in patients with and without AF. Atrial fibrillation was a significant predictor of CD in patients with normal (1.6% per year vs. 0.4% per year in non-AF patients), mildly abnormal (6.3% per year vs. 1.2% per year), and severely abnormal MPS (6.4% per year vs. 3.7% per year) (p < 0.001 for all). By multivariable analysis, AF patients had worse survival (p = 0.001) even after adjustment for the variables most predictive of CD: age, diabetes, shortness of breath, use of vasodilator stress, rest heart rate, and the nuclear variables. In the 4,239 patients with left ventricular ejection fraction evaluated by gated MPS, AF demonstrated incremental prognostic value not only over clinical and nuclear variables, but also over left ventricular ejection in predicting CD (p = 0.014). The presence of AF independently increases the risk of cardiac events over perfusion and function variables in patients undergoing MPS. Patients with AF have a high risk of CD, even when MPS is only mildly abnormal. Whether patients with AF and mildly abnormal MPS constitute a group more deserving of early referral to cardiac catheterization is a question warranting further study.

  8. Quantitative Analysis of {sup 18}F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

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    Cui, Yi [Department of Radiation Oncology, Stanford University, Palo Alto, California (United States); Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo (Japan); Song, Jie; Pollom, Erqi; Alagappan, Muthuraman [Department of Radiation Oncology, Stanford University, Palo Alto, California (United States); Shirato, Hiroki [Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo (Japan); Chang, Daniel T.; Koong, Albert C. [Department of Radiation Oncology, Stanford University, Palo Alto, California (United States); Stanford Cancer Institute, Stanford, California (United States); Li, Ruijiang, E-mail: rli2@stanford.edu [Department of Radiation Oncology, Stanford University, Palo Alto, California (United States); Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo (Japan); Stanford Cancer Institute, Stanford, California (United States)

    2016-09-01

    Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT {sup 18}F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162 robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6

  9. Excision Repair Cross-complementation Group 1 is a Prognostic Biomarker in Patients with Colorectal Cancer Receiving Chemotherapy

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    Mu-Xing Li

    2016-01-01

    Conclusions: ERCC1 expression may be taken as an effective prognostic factor predicting the response to chemotherapy, OS, and PFS. Further studies with better study design and longer follow-up are warranted in order to gain a deeper understanding of ERCC1's prognostic value.

  10. Using image analysis as a tool for assessment of prognostic and predictive biomarkers for breast cancer: How reliable is it?

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    Mark C Lloyd

    2010-01-01

    Full Text Available Background : Estrogen receptor (ER, progesterone receptor (PR and human epidermal growth factor receptor-2 (HER2 are important and well-established prognostic and predictive biomarkers for breast cancers and routinely tested on patient′s tumor samples by immunohistochemical (IHC study. The accuracy of these test results has substantial impact on patient management. A critical factor that contributes to the result is the interpretation (scoring of IHC. This study investigates how computerized image analysis can play a role in a reliable scoring, and identifies potential pitfalls with common methods. Materials and Methods : Whole slide images of 33 invasive ductal carcinoma (IDC (10 ER and 23 HER2 were scored by pathologist under the light microscope and confirmed by another pathologist. The HER2 results were additionally confirmed by fluorescence in situ hybridization (FISH. The scoring criteria were adherent to the guidelines recommended by the American Society of Clinical Oncology/College of American Pathologists. Whole slide stains were then scored by commercially available image analysis algorithms from Definiens (Munich, Germany and Aperio Technologies (Vista, CA, USA. Each algorithm was modified specifically for each marker and tissue. The results were compared with the semi-quantitative manual scoring, which was considered the gold standard in this study. Results : For HER2 positive group, each algorithm scored 23/23 cases within the range established by the pathologist. For ER, both algorithms scored 10/10 cases within range. The performance of each algorithm varies somewhat from the percentage of staining as compared to the pathologist′s reading. Conclusions : Commercially available computerized image analysis can be useful in the evaluation of ER and HER2 IHC results. In order to achieve accurate results either manual pathologist region selection is necessary, or an automated region selection tool must be employed. Specificity can

  11. Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF-1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue.

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    Zhang, Lirong; Hu, Yu; Xi, Ning; Song, Jie; Huang, Wenjing; Song, Shanshan; Liu, Yiting; Liu, Xianying; Xie, Yingjun

    2016-01-01

    Hypoxia is prognostically important in colorectal cancer (CRC) therapy. Partial oxygen pressure (pO 2 ) is an important parameter of hypoxia. The correlation between pO 2 levels and expression levels of prognostic biomarkers was measured in CRC tissues. Human CRC tissues were collected and pO 2 levels were measured by OxyLite. Three methods for tissue fixation were compared, including formalin, Finefix, and Finefix-plus-microwave. Immunohistochemistry (IHC) staining was conducted by using the avidin-biotin complex technique for detecting the antibodies to hypoxia inducible factor-1 (HIF-1) alpha, cytokeratin 20 (CK20), and cell proliferation factor Ki67. The levels of pO 2 were negatively associated with the size of CRC tissues. Finefix-plus-microwave fixation has the potential to replace formalin. Additionally, microwave treatment improved Finefix performance in tissue fixation and protein preservation. The percentage of positive cells and gray values of HIF-1 alpha, CK20, and Ki67 were associated with CRC development ( P < 0.05). The levels of pO 2 were positively related with the gray values of Ki67 and negatively related with the values of HIF-1 alpha and CK20 ( P < 0.05). Thus, the levels of microenvironmental pO 2 affect the expression of predictive biomarkers HIF-1 alpha, CK20, and Ki67 in the development of CRC tissues.

  12. Data for iTRAQ profiling of micro-vesicular plasma specimens: In search of potential prognostic circulatory biomarkers for Lacunar infarction

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    Arnab Datta

    2015-09-01

    Full Text Available To discover potential prognostic biomarkers of Lacunar infarction (LACI, here we present quantitative proteomics data of plasma microvesicle-enriched fraction derived by comparative isobaric profiling of three groups of prospectively followed-up LACI patients (LACI – no adverse outcome, LACI –recurrent vascular event and LACI – cognitive decline and a demographically matched control group. We confidently (unused prot score >3, FDR=1.1% identified 183 proteins, 43 out of which were significantly regulated (p-value<0.05 in at least one of the three LACI groups in comparison to control group. Bioinformatics analysis and data mining revealed upregulation of brain-specific proteins including myelin basic protein, proteins of coagulation cascade (e.g., fibrinogen alpha chain, fibrinogen beta chain and focal adhesion (e.g., integrin alpha-IIb, talin-1, and filamin-A while albumin was downregulated in both groups of patients with adverse outcome. The data of this study are also in line with our previously published article entitled “Discovery of prognostic biomarker candidates of Lacunar infarction by quantitative proteomics of microvesicles enriched plasma” by Datta et al. (2014. The raw data had been deposited to the ProteomeXchange consortium with identifier PXD000748.

  13. Partial Oxygen Pressure Affects the Expression of Prognostic Biomarkers HIF-1 Alpha, Ki67, and CK20 in the Microenvironment of Colorectal Cancer Tissue

    Directory of Open Access Journals (Sweden)

    Lirong Zhang

    2016-01-01

    Full Text Available Hypoxia is prognostically important in colorectal cancer (CRC therapy. Partial oxygen pressure (pO2 is an important parameter of hypoxia. The correlation between pO2 levels and expression levels of prognostic biomarkers was measured in CRC tissues. Human CRC tissues were collected and pO2 levels were measured by OxyLite. Three methods for tissue fixation were compared, including formalin, Finefix, and Finefix-plus-microwave. Immunohistochemistry (IHC staining was conducted by using the avidin-biotin complex technique for detecting the antibodies to hypoxia inducible factor-1 (HIF-1 alpha, cytokeratin 20 (CK20, and cell proliferation factor Ki67. The levels of pO2 were negatively associated with the size of CRC tissues. Finefix-plus-microwave fixation has the potential to replace formalin. Additionally, microwave treatment improved Finefix performance in tissue fixation and protein preservation. The percentage of positive cells and gray values of HIF-1 alpha, CK20, and Ki67 were associated with CRC development (P<0.05. The levels of pO2 were positively related with the gray values of Ki67 and negatively related with the values of HIF-1 alpha and CK20 (P<0.05. Thus, the levels of microenvironmental pO2 affect the expression of predictive biomarkers HIF-1 alpha, CK20, and Ki67 in the development of CRC tissues.

  14. Systematic assessment of cervical cancer initiation and progression uncovers genetic panels for deep learning-based early diagnosis and proposes novel diagnostic and prognostic biomarkers.

    Science.gov (United States)

    Long, Nguyen Phuoc; Jung, Kyung Hee; Yoon, Sang Jun; Anh, Nguyen Hoang; Nghi, Tran Diem; Kang, Yun Pyo; Yan, Hong Hua; Min, Jung Eun; Hong, Soon-Sun; Kwon, Sung Won

    2017-12-12

    Although many outstanding achievements in the management of cervical cancer (CxCa) have obtained, it still imposes a major burden which has prompted scientists to discover and validate new CxCa biomarkers to improve the diagnostic and prognostic assessment of CxCa. In this study, eight different gene expression data sets containing 202 cancer, 115 cervical intraepithelial neoplasia (CIN), and 105 normal samples were utilized for an integrative systems biology assessment in a multi-stage carcinogenesis manner. Deep learning-based diagnostic models were established based on the genetic panels of intrinsic genes of cervical carcinogenesis as well as on the unbiased variable selection approach. Survival analysis was also conducted to explore the potential biomarker candidates for prognostic assessment. Our results showed that cell cycle, RNA transport, mRNA surveillance, and one carbon pool by folate were the key regulatory mechanisms involved in the initiation, progression, and metastasis of CxCa. Various genetic panels combined with machine learning algorithms successfully differentiated CxCa from CIN and normalcy in cross-study normalized data sets. In particular, the 168-gene deep learning model for the differentiation of cancer from normalcy achieved an externally validated accuracy of 97.96% (99.01% sensitivity and 95.65% specificity). Survival analysis revealed that ZNF281 and EPHB6 were the two most promising prognostic genetic markers for CxCa among others. Our findings open new opportunities to enhance current understanding of the characteristics of CxCa pathobiology. In addition, the combination of transcriptomics-based signatures and deep learning classification may become an important approach to improve CxCa diagnosis and management in clinical practice.

  15. Metabolic Tumor Volume as a Prognostic Imaging-Based Biomarker for Head-and-Neck Cancer: Pilot Results From Radiation Therapy Oncology Group Protocol 0522

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    Schwartz, David L., E-mail: david.schwartz@utsw.edu [Department of Radiation Oncology, University of Texas Southwestern School of Medicine, Dallas, Texas (United States); Harris, Jonathan [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Yao, Min [Department of Radiation Oncology, Case Western Reserve University School of Medicine, Cleveland, Ohio (United States); Rosenthal, David I. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Opanowski, Adam; Levering, Anthony [American College of Radiology Imaging Network, Philadelphia, Pennsylvania (United States); Ang, K. Kian [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Trotti, Andy M. [Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida (United States); Garden, Adam S. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Jones, Christopher U. [Sutter Medical Group, Sacramento, California (United States); Harari, Paul [Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States); Foote, Robert [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Holland, John [Department of Radiation Medicine, Oregon Health & Science University, Portland, Oregon (United States); Zhang, Qiang [Radiation Therapy Oncology Group Statistical Center, Philadelphia, Pennsylvania (United States); Le, Quynh-Thu [Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California (United States)

    2015-03-15

    Purpose: To evaluate candidate fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) imaging biomarkers for head-and-neck chemoradiotherapy outcomes in the cooperative group trial setting. Methods and Materials: Radiation Therapy Oncology Group (RTOG) protocol 0522 patients consenting to a secondary FDG-PET/CT substudy were serially imaged at baseline and 8 weeks after radiation. Maximum standardized uptake value (SUVmax), SUV peak (mean SUV within a 1-cm sphere centered on SUVmax), and metabolic tumor volume (MTV) using 40% of SUVmax as threshold were obtained from primary tumor and involved nodes. Results: Of 940 patients entered onto RTOG 0522, 74 were analyzable for this substudy. Neither high baseline SUVmax nor SUVpeak from primary or nodal disease were associated with poor treatment outcomes. However, primary tumor MTV above the cohort median was associated with worse local-regional control (hazard ratio 4.01, 95% confidence interval 1.28-12.52, P=.02) and progression-free survival (hazard ratio 2.34, 95% confidence interval 1.02-5.37, P=.05). Although MTV and T stage seemed to correlate (mean MTV 6.4, 13.2, and 26.8 for T2, T3, and T4 tumors, respectively), MTV remained a strong independent prognostic factor for progression-free survival in bivariate analysis that included T stage. Primary MTV remained prognostic in p16-associated oropharyngeal cancer cases, although sample size was limited. Conclusion: High baseline primary tumor MTV was associated with worse treatment outcomes in this limited patient subset of RTOG 0522. Additional confirmatory work will be required to validate primary tumor MTV as a prognostic imaging biomarker for patient stratification in future trials.

  16. CDO1 promoter methylation is associated with gene silencing and is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients.

    Science.gov (United States)

    Meller, Sebastian; Zipfel, Lisa; Gevensleben, Heidrun; Dietrich, Jörn; Ellinger, Jörg; Majores, Michael; Stein, Johannes; Sailer, Verena; Jung, Maria; Kristiansen, Glen; Dietrich, Dimo

    2016-12-01

    Molecular biomarkers may facilitate the distinction between aggressive and clinically insignificant prostate cancer (PCa), thereby potentially aiding individualized treatment. We analyzed cysteine dioxygenase 1 (CDO1) promoter methylation and mRNA expression in order to evaluate its potential as prognostic biomarker. CDO1 methylation and mRNA expression were determined in cell lines and formalin-fixed paraffin-embedded prostatectomy specimens from a first cohort of 300 PCa patients using methylation-specific qPCR and qRT-PCR. Univariate and multivariate Cox proportional hazards and Kaplan-Meier analyses were performed to evaluate biochemical recurrence (BCR)-free survival. Results were confirmed in an independent second cohort comprising 498 PCa cases. Methylation and mRNA expression data from the second cohort were generated by The Cancer Genome Atlas (TCGA) Research Network by means of Infinium HumanMethylation450 BeadChip and RNASeq. CDO1 was hypermethylated in PCa compared to normal adjacent tissues and benign prostatic hyperplasia (P < 0.001) and was associated with reduced gene expression (ρ = -0.91, P = 0.005). Using two different methodologies for methylation quantification, high CDO1 methylation as continuous variable was associated with BCR in univariate analysis (first cohort: HR = 1.02, P = 0.002, 95% CI [1.01-1.03]; second cohort: HR = 1.02, P = 0.032, 95% CI [1.00-1.03]) but failed to reach statistical significance in multivariate analysis. CDO1 promoter methylation is involved in gene regulation and is a potential prognostic biomarker for BCR-free survival in PCa patients following radical prostatectomy. Further studies are needed to validate CDO1 methylation assays and to evaluate the clinical utility of CDO1 methylation for the management of PCa.

  17. Prognostic value of bone- and vascular-derived molecular biomarkers in hemodialysis and renal transplant patients: a systematic review and meta-analysis.

    Science.gov (United States)

    Pichler, Gernot; Haller, Maria C; Kainz, Alexander; Wolf, Myles; Redon, Josep; Oberbauer, Rainer

    2017-09-01

    Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin (OPN), Klotho protein and bone morphogenetic protein-7 (BMP-7) are bone- and vascular-derived molecular biomarkers that have been shown to be associated with cardiovascular surrogate end points; however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data [hazard Ratio (HR)] or as effect size with a fixed time of follow-up [odds Ratio (OR)]. Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline FGF23 distribution, pooled HRs (95% confidence intervals) were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline OPG distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality. Reported risk estimates of RANK ligand, OPN, Klotho protein and BMP-7 were not suitable for pooling; however, only Klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of FGF23 and OPG with mortality were identified, all of which reported a significant association. In hemodialysis patients, FGF23 is a

  18. Bone Marrow Stromal Antigen 2 Is a Novel Plasma Biomarker and Prognosticator for Colorectal Carcinoma: A Secretome-Based Verification Study

    Directory of Open Access Journals (Sweden)

    Sum-Fu Chiang

    2015-01-01

    Full Text Available Background. The cancer cell secretome has been recognized as a valuable reservoir for identifying novel serum/plasma biomarkers for different cancers, including colorectal cancer (CRC. This study aimed to verify four CRC cell-secreted proteins (tumor-associated calcium signal transducer 2/trophoblast cell surface antigen 2 (TACSTD2/TROP2, tetraspanin-6 (TSPAN6, bone marrow stromal antigen 2 (BST2, and tumor necrosis factor receptor superfamily member 16 (NGFR as potential plasma CRC biomarkers. Methods. The study population comprises 152 CRC patients and 152 controls. Target protein levels in plasma and tissue samples were assessed by ELISA and immunohistochemistry, respectively. Results. Among the four candidate proteins examined by ELISA in a small sample set, only BST2 showed significantly elevated plasma levels in CRC patients versus controls. Immunohistochemical analysis revealed the overexpression of BST2 in CRC tissues, and higher BST2 expression levels correlated with poorer 5-year survival (46.47% versus 65.57%; p=0.044. Further verification confirmed the elevated plasma BST2 levels in CRC patients (2.35 ± 0.13 ng/mL versus controls (1.04 ± 0.03 ng/mL (p<0.01, with an area under the ROC curve (AUC being 0.858 comparable to that of CEA (0.867. Conclusion. BST2, a membrane protein selectively detected in CRC cell secretome, may be a novel plasma biomarker and prognosticator for CRC.

  19. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Che K

    2017-02-01

    Full Text Available Keying Che,1,* Yang Zhao,2,3,* Xiao Qu,1 Zhaofei Pang,1 Yang Ni,4 Tiehong Zhang,4 Jiajun Du,1,5 Hongchang Shen4 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 2Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Gastric carcinoma (GC is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.Materials and methods: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS was statistically analyzed.Results: Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145 of them. Single cell invasion and large cell invasion were observed in 62.8% (186 and 16.9% (50 of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0

  20. EPID-28. PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN

    DEFF Research Database (Denmark)

    Toft, Anders; Urup, Thomas; Grunnet, Kirsten

    2015-01-01

    BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The prim......BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients...... response MRI (RANO criteria). Responders had significantly prolonged OS (p ¼ 0.007) and trended toward longer PFS (p ¼ 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS: 5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence of necrosis were significantly more common...... in responders than nonresponders. Multivariate analysis also identified a poor PS as the only prognostic factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation were prognostic of reducedOS.CONCLUSIONS:Apoor baseline PS and the presence of necrosis were negatively associated...

  1. PD-L1 Is a Therapeutic Target of the Bromodomain Inhibitor JQ1 and, Combined with HLA Class I, a Promising Prognostic Biomarker in Neuroblastoma.

    Science.gov (United States)

    Melaiu, Ombretta; Mina, Marco; Chierici, Marco; Boldrini, Renata; Jurman, Giuseppe; Romania, Paolo; D'Alicandro, Valerio; Benedetti, Maria C; Castellano, Aurora; Liu, Tao; Furlanello, Cesare; Locatelli, Franco; Fruci, Doriana

    2017-08-01

    Purpose: This study sought to evaluate the expression of programmed cell death-ligand-1 (PD-L1) and HLA class I on neuroblastoma cells and programmed cell death-1 (PD-1) and lymphocyte activation gene 3 (LAG3) on tumor-infiltrating lymphocytes to better define patient risk stratification and understand whether this tumor may benefit from therapies targeting immune checkpoint molecules. Experimental Design: In situ IHC staining for PD-L1, HLA class I, PD-1, and LAG3 was assessed in 77 neuroblastoma specimens, previously characterized for tumor-infiltrating T-cell density and correlated with clinical outcome. Surface expression of PD-L1 was evaluated by flow cytometry and IHC in neuroblastoma cell lines and tumors genetically and/or pharmacologically inhibited for MYC and MYCN. A dataset of 477 human primary neuroblastomas from GEO and ArrayExpress databases was explored for PD-L1, MYC, and MYCN correlation. Results: Multivariate Cox regression analysis demonstrated that the combination of PD-L1 and HLA class I tumor cell density is a prognostic biomarker for predicting overall survival in neuroblastoma patients ( P = 0.0448). MYC and MYCN control the expression of PD-L1 in neuroblastoma cells both in vitro and in vivo Consistently, abundance of PD-L1 transcript correlates with MYC expression in primary neuroblastoma. Conclusions: The combination of PD-L1 and HLA class I represents a novel prognostic biomarker for neuroblastoma. Pharmacologic inhibition of MYCN and MYC may be exploited to target PD-L1 and restore an efficient antitumor immunity in high-risk neuroblastoma. Clin Cancer Res; 23(15); 4462-72. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    Directory of Open Access Journals (Sweden)

    Laura Muinelo-Romay

    2014-01-01

    Full Text Available In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC and their utility for therapy monitoring in non-small cell lung cancer (NSCLC. A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells were counted. At baseline 18 (41.9% patients were positive for intact CTC count and 10 (23.2% of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively. Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  3. Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Muinelo-Romay, Laura; Vieito, Maria; Abalo, Alicia; Alonso Nocelo, Marta; Barón, Francisco; Anido, Urbano; Brozos, Elena; Vázquez, Francisca; Aguín, Santiago; Abal, Miguel; López López, Rafael, E-mail: rafael.lopez.lopez@sergas.es [Translational Medical Oncology, Health Research Institute of Santiago (IDIS), Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Trav. Choupana s/n 15706 Santiago de Compostela (Spain)

    2014-01-21

    In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ≥5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other “objects” such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

  4. Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis

    OpenAIRE

    Makis, Alexandros; Gkoutsias, Athanasios; Palianopoulos, Theodoros; Pappa, Eleni; Papapetrou, Evangelia; Tsaousi, Christina; Hatzimichael, Eleftheria; Chaliasos, Nikolaos

    2017-01-01

    Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and ...

  5. Evaluation of miR-21 and miR-375 as prognostic biomarkers in esophageal cancer

    DEFF Research Database (Denmark)

    Winther, Mette; Alsner, Jan; Tramm, Trine

    2015-01-01

    analyses identified miR-21 as an independent prognostic marker for DSS in EAC [HR 3.52 (95% CI 1.06-11.69)]. High miR-375 was not correlated with improved prognosis in either histology. However, Forest plots demonstrated that both miR-21 and miR-375 were of prognostic impact in ESCC. CONCLUSION...... chemotherapy were analyzed. Expression levels of miR-21 and miR-375 were quantified using Affymetrix GeneChip miRNA 1.0 Array. The Cox proportional hazards model was used to assess the correlation of miR-21 and miR-375 with disease-specific survival (DSS) and overall survival (OS). Forest plots were performed...... to evaluate the prognostic impact of miR-21 and miR-375 in the present study and previously published reports. RESULTS: In ESCC, patients with miR-21 expression levels above median showed a trend towards poorer DSS and OS. When dividing miR-21 expression by tertiles, high levels of miR-21 significantly...

  6. Prognostic Impact of Inflammation-related Biomarkers on Overall Survival of Patients with Inoperable Malignant Pleural Mesothelioma.

    Science.gov (United States)

    Otoshi, Takehiro; Kataoka, Yuki; Kaku, Sawako; Iki, Reika; Hirabayashi, Masataka

    2018-01-01

    The aim of the present study was to assess the prognostic utility of the pretreatment blood neutrophil-to-lymphocyte ratio (NLR) and the C-reactive protein-to-albumin ratio (CAR) in patients with inoperable malignant pleural mesothelioma (MPM). The medical records of consecutive patients with histologically confirmed MPM from our hospital between January 2007 and August 2017 were retrospectively reviewed. The primary outcome was overall survival (OS). Univariate and multivariate analyses for the prognostic factors were performed using a Cox proportional hazards model. A total of 143 patients with inoperable MPM were included. On multivariate analysis, pretreatment CAR was an independent factor associated with worse OS (hazard ratio(HR)=1.72; 95% confidence interval(CI)=1.11-2.67; p=0.016). However, NLR was not associated with OS in any of the analyses. CAR appears to be a prognostic factor in patients with inoperable MPM. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  7. Is Ep-CAM Expression a Diagnostic and Prognostic Biomarker for Colorectal Cancer? A Systematic Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Susu Han

    2017-06-01

    Conclusions: The present findings suggest that Ep-CAM expression may be associated with CRC carcinogenesis, while the loss of Ep-CAM expression is correlated with the progression, metastasis, and poor prognosis of CRC. Ep-CAM expression may be a useful biomarker for the clinical diagnosis of CRC.

  8. Assessing EphA2 and Ephrin-A as Novel Diagnostic and Prognostic Biomarkers of Prostate Cancer

    Science.gov (United States)

    2017-10-01

    to facilitate optimal treatment selection for each patient; 3) Elucidation of the biological mechanisms behind the PCa health disparities that...affect minority men. During this last study period, we have enrolled 20 additional male patients into our study. We have optimized the RNA isolation... health disparities that affect African American men. 2. KEYWORDS: prostate cancer, biomarkers, racial disparity, health outcomes 3. ACCOMPLISHMENTS

  9. Evaluation of Shape and Textural Features from CT as Prognostic Biomarkers in Non-small Cell Lung Cancer.

    Science.gov (United States)

    Bianconi, Francesco; Fravolini, Mario Luca; Bello-Cerezo, Raquel; Minestrini, Matteo; Scialpi, Michele; Palumbo, Barbara

    2018-04-01

    We retrospectively investigated the prognostic potential (correlation with overall survival) of 9 shape and 21 textural features from non-contrast-enhanced computed tomography (CT) in patients with non-small-cell lung cancer. We considered a public dataset of 203 individuals with inoperable, histologically- or cytologically-confirmed NSCLC. Three-dimensional shape and textural features from CT were computed using proprietary code and their prognostic potential evaluated through four different statistical protocols. Volume and grey-level run length matrix (GLRLM) run length non-uniformity were the only two features to pass all four protocols. Both features correlated negatively with overall survival. The results also showed a strong dependence on the evaluation protocol used. Tumour volume and GLRLM run-length non-uniformity from CT were the best predictor of survival in patients with non-small-cell lung cancer. We did not find enough evidence to claim a relationship with survival for the other features. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  10. Outcome and prognostic factors in single brain metastases from small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Bernhardt, Denise; Koenig, Laila [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Adeberg, Sebastian; Debus, Juergen [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Radiation Oncology, Heidelberg (Germany); Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg (Germany); Bozorgmehr, Farastuk; Thomas, Michael; Steins, Martin [Heidelberg University, Department of Thoracic Oncology, Thoraxklinik, Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Opfermann, Nils; Hoerner-Rieber, Juliane; Rieken, Stefan [University Hospital Heidelberg, Department of Radiation Oncology, INF 400, Heidelberg (Germany); Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg (Germany); Kappes, Jutta [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); Unterberg, Andreas [University Hospital Heidelberg, Department of Neurosurgery, INF 400, Heidelberg (Germany); Herth, Felix [Heidelberg University, Department of Pneumology, Thoraxklinik, Heidelberg (Germany); German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); Heussel, Claus Peter [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology with Nuclear Medicine, Thoraxklinik, Heidelberg (Germany); University of Heidelberg, Diagnostic and Interventional Radiology, Heidelberg (Germany); Warth, Arne [German Centre for Lung Research (DZL), Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg (DE); Heidelberg University, Institute of Pathology, Heidelberg (DE)

    2018-02-15

    Whole brain radiation therapy (WBRT) is historically the standard of care for patients with brain metastases (BM) from small-cell lung cancer (SCLC), although locally ablative treatments are the standard of care for patients with 1-4 BM from other solid tumors. The objective of this analysis was to find prognostic factors influencing overall survival (OS) and intracranial progression-free survival (iPFS) in SCLC patients with single BM (SBM) treated with WBRT. A total of 52 patients were identified in the authors' cancer center database with histologically confirmed SCLC and contrast-enhanced magnet resonance imaging (MRI) or computed tomography (CT), which confirmed SBM between 2006 and 2015 and were therefore treated with WBRT. A Kaplan-Meier survival analysis was performed for OS analyses. The log-rank (Mantel-Cox) test was used to compare survival curves. Univariate Cox proportional-hazards ratios (HRs) were used to assess the influence of cofactors on OS and iPFS. The median OS after WBRT was 5 months and the median iPFS after WBRT 16 months. Patients that received surgery prior to WBRT had a significantly longer median OS of 19 months compared to 5 months in the group receiving only WBRT (p = 0.03; HR 2.24; 95% confidence interval [CI] 1.06-4.73). Patients with synchronous disease had a significantly longer OS compared to patients with metachronous BM (6 months vs. 3 months, p = 0.005; HR 0.27; 95% CI 0.11-0.68). Univariate analysis for OS revealed a statistically significant effect for metachronous disease (HR 2.25; 95% CI 1.14-4.46; p = 0.019), initial response to first-line chemotherapy (HR 0.58; 95% CI 0.35-0.97; p = 0.04), and surgical resection (HR 0.36; 95% CI 0.15-0.88; p = 0.026). OS was significantly affected by metachronous disease in multivariate analysis (HR 2.20; 95% CI 1.09-4.45; p = 0.028). Univariate analysis revealed that surgery followed by WBRT can improve OS in patients with SBM in SCLC. Furthermore, synchronous disease and response

  11. Identification of rheumatoid arthritis biomarkers based on single nucleotide polymorphisms and haplotype blocks: A systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Mohamed N. Saad

    2016-01-01

    Full Text Available Genetics of autoimmune diseases represent a growing domain with surpassing biomarker results with rapid progress. The exact cause of Rheumatoid Arthritis (RA is unknown, but it is thought to have both a genetic and an environmental bases. Genetic biomarkers are capable of changing the supervision of RA by allowing not only the detection of susceptible individuals, but also early diagnosis, evaluation of disease severity, selection of therapy, and monitoring of response to therapy. This review is concerned with not only the genetic biomarkers of RA but also the methods of identifying them. Many of the identified genetic biomarkers of RA were identified in populations of European and Asian ancestries. The study of additional human populations may yield novel results. Most of the researchers in the field of identifying RA biomarkers use single nucleotide polymorphism (SNP approaches to express the significance of their results. Although, haplotype block methods are expected to play a complementary role in the future of that field.

  12. Can Vascular Endothelial Growth Factor and Microvessel Density Be Used as Prognostic Biomarkers for Colorectal Cancer? A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Yibaina Wang

    2014-01-01

    Full Text Available Background. Vascular endothelial growth factor (VEGF and microvessel density (MVD are associated with greater incidence of metastases and decreased survival. Whether they can be used as prognostic indicators of colorectal cancer (CRC is still controversial. Methods. The authors performed a meta-analysis using the results of a literature search of databases of PubMed and EMBASE, and the references of articles included in the analysis. Meta-analysis was performed using random effects model and hazard ratios (HRs and 95% confidence intervals (CIs as effect measures. Results. Twenty studies contributed to the analysis of VEGF, of which 16 were used for overall survival (OS and 9 for disease-free survival (DFS. High VEGF levels has a relationship with unfavorable survival (OS: HR = 1.98, 95% CI: 1.30–3.02; DFS: HR = 2.10, 95% CI: 1.26–3.49 and a 4.22-fold increase in the rate of distant metastases. Analysis was performed on 18 studies for MVD; the results showed that patients with high MVD expression in tumors appeared to have poorer overall survival (HR = 1.39, 95% CI: 1.22–1.58 and were at a greater risk of having unfavorable clinical characteristics related to prognosis. Corresponding results were obtained from quantitative and/or qualitative analysis of clinicopathological. Conclusions. The meta-analysis demonstrates that VEGF and MVD can be used as prognostic biomarkers for CRC patients.

  13. Multistream sensor fusion-based prognostics model for systems with single failure modes

    International Nuclear Information System (INIS)

    Fang, Xiaolei; Paynabar, Kamran; Gebraeel, Nagi

    2017-01-01

    Advances in sensor technology have facilitated the capability of monitoring the degradation of complex engineering systems through the analysis of multistream degradation signals. However, the varying levels of correlation with physical degradation process for different sensors, high-dimensionality of the degradation signals and cross-correlation among different signal streams pose significant challenges in monitoring and prognostics of such systems. To address the foregoing challenges, we develop a three-step multi-sensor prognostic methodology that utilizes multistream signals to predict residual useful lifetimes of partially degraded systems. We first identify the informative sensors via the penalized (log)-location-scale regression. Then, we fuse the degradation signals of the informative sensors using multivariate functional principal component analysis, which is capable of modeling the cross-correlation of signal streams. Finally, the third step focuses on utilizing the fused signal features for prognostics via adaptive penalized (log)-location-scale regression. We validate our multi-sensor prognostic methodology using simulation study as well as a case study of aircraft turbofan engines available from NASA repository.

  14. APOBEC3A is an oral cancer prognostic biomarker in Taiwanese carriers of an APOBEC deletion polymorphism.

    Science.gov (United States)

    Chen, Ting-Wen; Lee, Chi-Ching; Liu, Hsuan; Wu, Chi-Sheng; Pickering, Curtis R; Huang, Po-Jung; Wang, Jing; Chang, Ian Yi-Feng; Yeh, Yuan-Ming; Chen, Chih-De; Li, Hsin-Pai; Luo, Ji-Dung; Tan, Bertrand Chin-Ming; Chan, Timothy En Haw; Hsueh, Chuen; Chu, Lichieh Julie; Chen, Yi-Ting; Zhang, Bing; Yang, Chia-Yu; Wu, Chih-Ching; Hsu, Chia-Wei; See, Lai-Chu; Tang, Petrus; Yu, Jau-Song; Liao, Wei-Chao; Chiang, Wei-Fan; Rodriguez, Henry; Myers, Jeffrey N; Chang, Kai-Ping; Chang, Yu-Sun

    2017-09-06

    Oral squamous cell carcinoma is a prominent cancer worldwide, particularly in Taiwan. By integrating omics analyses in 50 matched samples, we uncover in Taiwanese patients a predominant mutation signature associated with cytidine deaminase APOBEC, which correlates with the upregulation of APOBEC3A expression in the APOBEC3 gene cluster at 22q13. APOBEC3A expression is significantly higher in tumors carrying APOBEC3B-deletion allele(s). High-level APOBEC3A expression is associated with better overall survival, especially among patients carrying APOBEC3B-deletion alleles, as examined in a second cohort (n = 188; p = 0.004). The frequency of APOBEC3B-deletion alleles is ~50% in 143 genotyped oral squamous cell carcinoma -Taiwan samples (27A3B -/- :89A3B +/- :27A3B +/+ ), compared to the 5.8% found in 314 OSCC-TCGA samples. We thus report a frequent APOBEC mutational profile, which relates to a APOBEC3B-deletion germline polymorphism in Taiwanese oral squamous cell carcinoma that impacts expression of APOBEC3A, and is shown to be of clinical prognostic relevance. Our finding might be recapitulated by genomic studies in other cancer types.Oral squamous cell carcinoma is a prevalent malignancy in Taiwan. Here, the authors show that OSCC in Taiwanese show a frequent deletion polymorphism in the cytidine deaminases gene cluster APOBEC3 resulting in increased expression of A3A, which is shown to be of clinical prognostic relevance.

  15. Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer

    Directory of Open Access Journals (Sweden)

    Li Hai-gang

    2011-09-01

    Full Text Available Abstract Background 14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial. Methods The method of immunohistochemistry (IHC and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66. For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86 and overall patients (n = 152. Results The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS and progression-free survival (PFS. Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer. Conclusions These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor.

  16. Aberrant upregulation of 14-3-3ơ expression serves as an inferior prognostic biomarker for gastric cancer

    International Nuclear Information System (INIS)

    Zhou, Wei-hua; Tang, Fang; Xu, Jie; Wu, Xing; Feng, Zhi-ying; Li, Hai-gang; Lin, Dong-jun; Shao, Chun-kui; Liu, Quentin

    2011-01-01

    14-3-3ơ is an intracellular, phosphoserine binding protein and proposed to be involved in tumorigenesis. However, the expression dynamics of 14-3-3ơ and its clinicopathological/prognostic significance in human tumors are still controversial. The method of immunohistochemistry (IHC) and Western blot were utilized to examine the protein expression of 14-3-3ơ in gastric cancer and paired normal adjacent gastric mucosal tissues. Receive operating characteristic (ROC) curve analysis was employed to determine a cutoff score for 14-3-3ơ expression in a training set (n = 66). For validation, the ROC-derived cutoff score was subjected to analysis of the association of 14-3-3ơ expression with patient outcome and clinical characteristics in a testing set (n = 86) and overall patients (n = 152). The expression frequency and expression levels of 14-3-3ơ were significantly higher in gastric cancer than in normal gastric mucosal tissues. Correlation analysis demonstrated that high expression of 14-3-3ơ in gastric cancer was significantly correlated with clinical stage and tumor invasion. Furthermore, in the testing set and overall patients, Kaplan-Meier analysis showed that elevated 14-3-3ơ expression predicted poorer overall survival (OS) and progression-free survival (PFS). Importantly, high 14-3-3ơ expression was also associated with shortened survival time in stage III and stage IV gastric cancer patients. Multivariate analyses revealed that 14-3-3ơ expression was an independent prognostic parameter in gastric cancer. These findings provide evidence that high expression of 14-3-3ơ may be important in the tumor progression and servers as an independent molecular marker for poor prognosis of gastric cancer. Thus, overexpression of 14-3-3ơ identifies patients at high risk and is a novel therapeutic molecular target for this tumor

  17. Single nucleotide polymorphism array karyotyping: a diagnostic and prognostic tool in myelodysplastic syndromes with unsuccessful conventional cytogenetic testing.

    Science.gov (United States)

    Arenillas, Leonor; Mallo, Mar; Ramos, Fernando; Guinta, Kathryn; Barragán, Eva; Lumbreras, Eva; Larráyoz, María-José; De Paz, Raquel; Tormo, Mar; Abáigar, María; Pedro, Carme; Cervera, José; Such, Esperanza; José Calasanz, María; Díez-Campelo, María; Sanz, Guillermo F; Hernández, Jesús María; Luño, Elisa; Saumell, Sílvia; Maciejewski, Jaroslaw; Florensa, Lourdes; Solé, Francesc

    2013-12-01

    Cytogenetic aberrations identified by metaphase cytogenetics (MC) have diagnostic, prognostic, and therapeutic implications in myelodysplastic syndromes (MDS). However, in some MDS patients MC study is unsuccesful. Single nucleotide polymorphism array (SNP-A) based karyotyping could be helpful in these cases. We performed SNP-A in 62 samples from bone marrow or peripheral blood of primary MDS with an unsuccessful MC study. SNP-A analysis enabled the detection of aberrations in 31 (50%) patients. We used the copy number alteration information to apply the International Prognostic Scoring System (IPSS) and we observed differences in survival between the low/intermediate-1 and intermediate-2/high risk patients. We also saw differences in survival between very low/low/intermediate and the high/very high patients when we applied the revised IPSS (IPSS-R). In conclusion, SNP-A can be used successfully in PB samples and the identification of CNA by SNP-A improve the diagnostic and prognostic evaluation of this group of MDS patients. Copyright © 2013 Wiley Periodicals, Inc.

  18. Epigenome-Wide Tumor DNA Methylation Profiling Identifies Novel Prognostic Biomarkers of Metastatic-Lethal Progression in Men Diagnosed with Clinically Localized Prostate Cancer.

    Science.gov (United States)

    Zhao, Shanshan; Geybels, Milan S; Leonardson, Amy; Rubicz, Rohina; Kolb, Suzanne; Yan, Qingxiang; Klotzle, Brandy; Bibikova, Marina; Hurtado-Coll, Antonio; Troyer, Dean; Lance, Raymond; Lin, Daniel W; Wright, Jonathan L; Ostrander, Elaine A; Fan, Jian-Bing; Feng, Ziding; Stanford, Janet L

    2017-01-01

    Aside from Gleason sum, few factors accurately identify the subset of prostate cancer patients at high risk for metastatic progression. We hypothesized that epigenetic alterations could distinguish prostate tumors with life-threatening potential. Epigenome-wide DNA methylation profiling was performed in surgically resected primary tumor tissues from a population-based (n = 430) and a replication (n = 80) cohort of prostate cancer patients followed prospectively for at least 5 years. Metastasis was confirmed by positive bone scan, MRI, CT, or biopsy, and death certificates confirmed cause of death. AUC, partial AUC (pAUC, 95% specificity), and P value criteria were used to select differentially methylated CpG sites that robustly stratify patients with metastatic-lethal from nonrecurrent tumors, and which were complementary to Gleason sum. Forty-two CpG biomarkers stratified patients with metastatic-lethal versus nonrecurrent prostate cancer in the discovery cohort, and eight of these CpGs replicated in the validation cohort based on a significant (P prostate cancer include CpGs in five genes (ALKBH5, ATP11A, FHAD1, KLHL8, and PI15) and three intergenic regions. In the validation dataset, the AUC for Gleason sum alone (0.82) significantly increased with the addition of four individual CpGs (range, 0.86-0.89; all P epigenetic biomarkers warrant further investigation as they may improve prognostic classification of patients with clinically localized prostate cancer and provide new insights on tumor aggressiveness. Clin Cancer Res; 23(1); 311-9. ©2016 AACR. ©2016 American Association for Cancer Research.

  19. Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy

    DEFF Research Database (Denmark)

    Specht, L; Nordentoft, A M; Cold, Søren

    1987-01-01

    One hundred and forty-two patients with Hodgkin's disease PS I or II were treated with total or subtotal nodal irradiation as part of a prospective randomized trial in the Danish National Hodgkin Study during the period 1971-83. They were followed till death or--at the time of this analysis......--from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival...

  20. Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer.

    Science.gov (United States)

    Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung-Mo; Mullendore, Michael; Roa, Ivan; Ibañez, Luis; Pimentel, Fernando; Diaz, Alfonso; Riggins, Gregory J; Maitra, Anirban

    2008-05-01

    Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.

  1. Towards prognostic biomarkers from BOLD fluctuations to differentiate a first epileptic seizure from new-onset epilepsy.

    Science.gov (United States)

    Gupta, Lalit; Janssens, Rick; Vlooswijk, Mariëlle C G; Rouhl, Rob P W; de Louw, Anton; Aldenkamp, Albert P; Ulman, Shrutin; Besseling, René M H; Hofman, Paul A M; van Kranen-Mastenbroek, Vivianne H; Hilkman, Danny M; Jansen, Jacobus F A; Backes, Walter H

    2017-03-01

    The diagnosis of epilepsy cannot be reliably made prior to a patient's second seizure in most cases. Therefore, adequate diagnostic tools are needed to differentiate subjects with a first seizure from those with a seizure preceding the onset of epilepsy. The objective was to explore spontaneous blood oxygen level-dependent (BOLD) fluctuations in subjects with a first-ever seizure and patients with new-onset epilepsy (NOE), and to find characteristic biomarkers for seizure recurrence after the first seizure. We examined 17 first-seizure subjects, 19 patients with new-onset epilepsy (NOE), and 18 healthy controls. All subjects underwent clinical investigation and received electroencephalography and resting-state functional magnetic resonance imaging (MRI). The BOLD time series were analyzed in terms of regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFFs). We found significantly stronger amplitudes (higher fALFFs) in patients with NOE relative to first-seizure subjects and healthy controls. The frequency range of 73-198 mHz (slow-3 subband) appeared most useful for discriminating patients with NOE from first-seizure subjects. The ReHo measure did not show any significant differences. The fALFF appears to be a noninvasive measure that characterizes spontaneous BOLD fluctuations and shows stronger amplitudes in the slow-3 subband of patients with NOE relative first-seizure subjects and healthy controls. A larger study population with follow-up is required to determine whether fALFF holds promise as a potential biomarker for identifying subjects at increased risk to develop epilepsy. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  2. Urinary neutrophil-gelatinase associated lipocalin is a more prognostic biomarker to distinguish antenatal hydronephrosis in neonates

    Directory of Open Access Journals (Sweden)

    Hamid MohammadJafari

    2013-09-01

    Results: There was a significant difference in uNGAL concentration between AH patients and controls (0.80 ± 0.26 and 0.29 ± 0.27 ng/ml, p<0.0001. However, the levels of uNGAL was not significantly deviated between AH patients with VUR compared to those without VUR (0.84 ± 0.34 vs. 0.75 ± 0.13, p=0.419. Standardization of NGAL based on urinary creatinine (uNGAL/uCr showed a significantly difference between AH neonates with VUR compared to those without VUR (2.43±1.61 vs. 1.91±0.79, p<0.0001. Receiver operator characteristic (ROC analysis revealed higher prognostic power of uNGAL for identifying AH with a sensitivity 95.7%, and specificity 84.2%. Meanwhile, the levels of uNGAL or NGAL/uCr ratio did not correlate with reflux grade or laterality. Conclusion: The urinary level of NGAL and NGAL/uCr ratio might be a surrogate non invasive, reliable tool to distinguish hydronephrosis.

  3. Single-walled carbon nanotube based transparent immunosensor for detection of a prostate cancer biomarker osteopontin

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Abhinav; Hong, Seongkyeol; Singh, Renu [School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of); Jang, Jaesung, E-mail: jjang@unist.ac.kr [School of Mechanical and Nuclear Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of); Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of); School of Materials Science and Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan 689-798 (Korea, Republic of)

    2015-04-15

    Highlights: • A transparent CNT immunosensor is presented for detection of a prostate cancer biomarker osteopontin. • This immunosensor showed a highly linear and reproducible behavior from 1 pg mL{sup −1} to 1 μg mL{sup −1}. • The limit of detection of the immunosensor was 0.3 pg mL{sup −1}. • This immunosensor demonstrated high selectivity against bovine serum albumin and human serum. - Abstract: Osteopontin (OPN) is involved in almost all steps of cancer development, and it is being investigated as a potential biomarker for a diagnosis and prognosis of prostate cancer. Here, we report a label-free, highly sensitive and transparent immunosensor based on single-walled carbon nanotubes (SWCNTs) for detection of OPN. A high density of −COOH functionalized SWCNTs was deposited between two gold/indium tin oxide electrodes on a glass substrate by dielectrophoresis. Monoclonal antibodies specific to OPN were covalently immobilized on the SWCNTs. Relative resistance change of the immunosensors was measured as the concentration of OPN in phosphate buffer saline (PBS) and human serum was varied from 1 pg mL{sup −1} to 1 μg mL{sup −1} for different channel lengths of 2, 5, and 10 μm, showing a highly linear and reproducible behavior (R{sup 2} > 97%). These immunosensors were also specific to OPN against another test protein, bovine serum albumin, PBS and human serum, showing that a limit of detection for OPN was 0.3 pg mL{sup −1}. This highly sensitive and transparent immunosensor has a great potential as a simple point-of-care test kit for various protein biomarkers.

  4. Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution

    International Nuclear Information System (INIS)

    Hulshof, M.C.C.M.; Schimmel, E.C.; Gonzalez, D.G.; Koot, R.W.; Bosch, D.A.; Dekker, F.

    2001-01-01

    Background: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. Patients and method: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. Results: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. Conclusion: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors

  5. TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xin; Wan, Jin-Xiang; Ke, Zun-Ping; Wang, Feng; Chai, Hai-Xia; Liu, Jia-Qiang

    2017-07-01

    Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

  6. Treatment, Outcome and Prognostic Factors in Renal Cell Carcinoma - A Single Center Study (2000-2010)

    Science.gov (United States)

    Achermann, Christof; Stenner, Frank; Rothschild, Sacha I.

    2016-01-01

    In Switzerland efficient availability of novel drugs for renal cell cancer (RCC) has been granted early. Since the advent of the targeted agents for RCC the usage of these drugs has been reported to improve progression free survival. Here, we find that patients who are able to receive sequential targeted therapy, including tyrosine kinase inhibitors (TKI) and mTOR inhibitors (mTORi), have a largely better outcome than those who have less exposure to these agents. The value of the prognostic scores developed by Motzer and Heng is fully reflected by the outcomes according to prognostic risk groups in our unselected patient cohort. Also, the use of surgical intervention appears to be an important prognostic factor, however with a somehow diminished effect by novel systemic therapies. The importance of multiple lines of targeted therapies is underlined by this retrospective analysis. For patients with metastatic RCC not receiving targeted therapy the median OS was 22.6 months compared to those with one TKI 25.4 months. Patients receiving a second-line therapy (median overall survival 27.6 months) and those patients with three or more lines of therapy (43.8 months) have the greatest benefit. Also, exposure to a mTORi improves survival versus non-exposure to mTORi (63.3 vs. 22.3 months, p=0.038). In conclusion a trend towards improved survival is confirmed for an unselected population when the full variety of therapeutic options is available and can be used for the individual patient. PMID:27313782

  7. TU-CD-BRB-08: Radiomic Analysis of FDG-PET Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated with SBRT

    Energy Technology Data Exchange (ETDEWEB)

    Cui, Y; Shirato, H [Hokkaido University, Global Institute for Collaborative Research and Educat, Sapporo, Hokkaido (Japan); Song, J; Pollom, E; Chang, D; Koong, A [Stanford University, Palo Alto, CA (United States); Li, R [Hokkaido University, Global Institute for Collaborative Research and Educat, Sapporo, Hokkaido (Japan); Stanford University, Palo Alto, CA (United States)

    2015-06-15

    Purpose: This study aims to identify novel prognostic imaging biomarkers in locally advanced pancreatic cancer (LAPC) using quantitative, high-throughput image analysis. Methods: 86 patients with LAPC receiving chemotherapy followed by SBRT were retrospectively studied. All patients had a baseline FDG-PET scan prior to SBRT. For each patient, we extracted 435 PET imaging features of five types: statistical, morphological, textural, histogram, and wavelet. These features went through redundancy checks, robustness analysis, as well as a prescreening process based on their concordance indices with respect to the relevant outcomes. We then performed principle component analysis on the remaining features (number ranged from 10 to 16), and fitted a Cox proportional hazard regression model using the first 3 principle components. Kaplan-Meier analysis was used to assess the ability to distinguish high versus low-risk patients separated by median predicted survival. To avoid overfitting, all evaluations were based on leave-one-out cross validation (LOOCV), in which each holdout patient was assigned to a risk group according to the model obtained from a separate training set. Results: For predicting overall survival (OS), the most dominant imaging features were wavelet coefficients. There was a statistically significant difference in OS between patients with predicted high and low-risk based on LOOCV (hazard ratio: 2.26, p<0.001). Similar imaging features were also strongly associated with local progression-free survival (LPFS) (hazard ratio: 1.53, p=0.026) on LOOCV. In comparison, neither SUVmax nor TLG was associated with LPFS (p=0.103, p=0.433) (Table 1). Results for progression-free survival and distant progression-free survival showed similar trends. Conclusion: Radiomic analysis identified novel imaging features that showed improved prognostic value over conventional methods. These features characterize the degree of intra-tumor heterogeneity reflected on FDG

  8. Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis.

    Science.gov (United States)

    Makis, Alexandros; Gkoutsias, Athanasios; Palianopoulos, Theodoros; Pappa, Eleni; Papapetrou, Evangelia; Tsaousi, Christina; Hatzimichael, Eleftheria; Chaliasos, Nikolaos

    2017-01-01

    Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and platelets at diagnosis, treatment, disease course, and immunological markers was recorded. 39 children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP children were more likely to be of age > 10 years ( p = 0.015) and have gradual initiation of the disease ( p = 0.001), platelets > 10 × 10 9 /L ( p = 0.01), and impaired immunological markers ( p < 0.003) compared to newly diagnosed/persistent groups. Recent history of infection was found mainly in the newly diagnosed/persistent group ( p = 0.013). None of the children exhibited severe spontaneous bleeding. Conclusion . Even though ITP in children usually has a self-limited course, with rare serious bleeding complications, the chronic form of the disease is characterized by different predictive parameters, which can be used in clinical practice.

  9. Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis

    Directory of Open Access Journals (Sweden)

    Alexandros Makis

    2017-01-01

    Full Text Available Immune thrombocytopenia (ITP in children has a varied course and according to duration is distinguished as newly diagnosed (12 types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and platelets at diagnosis, treatment, disease course, and immunological markers was recorded. 39 children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP children were more likely to be of age > 10 years (p=0.015 and have gradual initiation of the disease (p=0.001, platelets > 10 × 109/L (p=0.01, and impaired immunological markers (p<0.003 compared to newly diagnosed/persistent groups. Recent history of infection was found mainly in the newly diagnosed/persistent group (p=0.013. None of the children exhibited severe spontaneous bleeding. Conclusion. Even though ITP in children usually has a self-limited course, with rare serious bleeding complications, the chronic form of the disease is characterized by different predictive parameters, which can be used in clinical practice.

  10. Exosomal miRNAs from Peritoneum Lavage Fluid as Potential Prognostic Biomarkers of Peritoneal Metastasis in Gastric Cancer.

    Directory of Open Access Journals (Sweden)

    Motohiko Tokuhisa

    Full Text Available Peritoneal metastasis is the most frequent type of recurrence in patients with gastric cancer (GC and is associated with poor prognosis. Peritoneal lavage cytology, used to evaluate the risk of peritoneal metastasis, has low sensitivity. Here, we assessed the diagnostic potential of exosomal miRNA profiles in peritoneal fluid for the prediction of peritoneal dissemination in GC. Total RNA was extracted from exosomes isolated from six gastric malignant ascites (MA samples, 24 peritoneal lavage fluid (PLF samples, and culture supernatants (CM of two human gastric carcinoma cell lines that differ in their potential for peritoneal metastasis. Expression of exosomal miRNAs was evaluated with Agilent Human miRNA microarrays and quantitative reverse transcription polymerase chain reaction (qRT-PCR. The microarray analysis indicated a low variability in the number and signal intensity of miRNAs detected among the samples. In the six MA fluids, miR-21 showed the highest signal intensity. We identified five miRNAs (miR-1225-5p, miR-320c, miR-1202, miR-1207-5p, and miR-4270 with high expression in MA samples, the PLF of serosa-invasive GC, and the CM of a highly metastatic GC cell line; these candidate miRNA species appear to be related to peritoneal dissemination. Differential expression of miR-21, miR-320c, and miR-1225-5p was validated in the PLF of serosa-invasive and non-invasive GC by qRT-PCR and miR-21 and miR-1225-5p were confirmed to be associated with serosal invasion in GC. PLF can be used to profile the expression of exosomal miRNAs. Our findings suggest that miR-21 and miR-1225-5p may serve as biomarkers of peritoneal recurrence after curative GC resection, thus providing a novel approach to early diagnosis of peritoneal dissemination of GC.

  11. Recipient Related Prognostic Factors for Graft Survival after Kidney Transplantation. A Single Center Experience

    Directory of Open Access Journals (Sweden)

    Alina Daciana ELEC

    2012-09-01

    Full Text Available Background and Aim. Advanced chronic kidney disease (CKD severely impairs life expectancy and quality of life in affected patients. Considering its benefits, renal transplantation currently represents the optimal treatment solution for end stage kidney disease patients. Pre-transplant assessment aims to maximize the graft and patient survival by identifying potential factors influencing the post-transplant outcome. The aim of this study has been to analyze recipient related prognostic factors bearing an impact on graft survival. Material and Methods. We analyzed the graft outcomes of 426 renal transplantations performed at the Clinical Institute of Urology and Renal Transplantation of Cluj-Napoca, between January 2004 and December 2008. Variables related to recipient and to potential donor/recipient prognostic factors were studied using univariate and multivariate analysis. Results. Graft survivals at 1, 3, 5 and 7 years were 94.01%, 88.37%, 82.51% and 78.10%, respectively. Chronic rejection (41.11% and death with a functioning graft (18.88% were the main causes of graft loss. In uni and multivariate analysis the recipient related variables found to influence the renal graft outcome were: peritoneal dialysis, pre transplant residual diuresis, grade I hypertension, severe iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition. The worst graft outcomes have been found for recipients on peritoneal dialysis, with anuria, hypotension, severe iliac atheromatosis, ischemic heart disease, stroke history, dyslipidemia and a poor nutritional status. Conclusion. The type of dialysis, the pre transplant residual diuresis, recipient arterial blood pressure, iliac vessel atheromatosis, ischemic heart disease, stroke history, dyslipidemia and denutrition significantly influence graft survival.

  12. Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325).

    Science.gov (United States)

    Dehing-Oberije, Cary; Aerts, Hugo; Yu, Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; van der Weide, Hiska; Rao, Bharat; Lambin, Philippe

    2011-10-01

    Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Prognostic factors in glioblastoma multiforme. 10 years experience of a single institution

    Energy Technology Data Exchange (ETDEWEB)

    Hulshof, M C.C.M.; Schimmel, E C; Gonzalez, D G [Amsterdam Univ. (Netherlands). Dept. of Radiotherapy; Koot, R W; Bosch, D A [Amsterdam Univ. (Netherlands). Dept. of Neurosurgery; Dekker, F [Amsterdam Univ. (Netherlands). Dept. of Epidemiology

    2001-06-01

    Background: To analyze prognostic factors in patients with a glioblastoma multiforme treated in an academic institute over the last 10 years. Patients and method: From 1988 to 1998, 198 patients with pathologically confirmed glioblastoma multiforme were analyzed. Five radiation schedules were used mainly based on pretreatment selection criteria: 1. 60 Gy in 30 fractions followed by an interstitial iridium-192 (Ir-192) boost for selected patients with a good performance and a small circumscribed tumor, 2. 66 Gy in 33 fractions for good performance patients, 3. 40 Gy in eight fractions or 4. 28 Gy in four fractions for poor prognostic patients and 5. no irradiation. Results: Median survival was 16 months, 7 months, 5.6 months, 6.6 months and 1.8 months for the groups treated with Ir-192, 66 Gy, 40 Gy, 28 Gy and the group without treatment, respectively. No significant improvement in survival was encountered over the last 10 years. At multivariate analysis patients treated with a hypofractionated scheme showed a similar survival probability and duration of palliative effect compared to the conventionally fractionated group. The poor prognostic groups receiving radiotherapy had a highly significant better survival compared to the no-treatment group. Patients treated with an Ir-192 boost had a better median survival compared to a historical group matched on selection criteria but without boost treatment (16 vs 9.7 months, n.s.). However, survival at 2 years was similar. Analysis on pretreatment characteristics at multivariate analysis revealed age, neurological performance, addition of radiotherapy, total resection, tumor size post surgery and deterioration before start of radiotherapy (borderline) as significant prognostic factors for survival. Conclusion: Despite technical developments in surgery and radiotherapy over the last 10 years, survival of patients with a glioblastoma multiforme has not improved in our institution. The analysis of prognostic factors

  14. CECs and IL-8 Have Prognostic and Predictive Utility in Patients with Recurrent Platinum-Sensitive Ovarian Cancer: Biomarker Correlates from the Randomized Phase-2 Trial of Olaparib and Cediranib Compared with Olaparib in Recurrent Platinum-Sensitive Ovarian Cancer.

    Science.gov (United States)

    Lee, Jung-Min; Trepel, Jane B; Choyke, Peter; Cao, Liang; Sissung, Tristan; Houston, Nicole; Yu, Minshu; Figg, William D; Turkbey, Ismail Baris; Steinberg, Seth M; Lee, Min-Jung; Ivy, S Percy; Liu, Joyce F; Matulonis, Ursula A; Kohn, Elise C

    2015-01-01

    Olaparib (O), a polyADPribose polymerase (PARP) inhibitor, and cediranib (C), a VEGF receptor (VEGFR)1-3 inhibitor together had greater activity than O alone in women with recurrent platinum-sensitive ovarian cancer (OvCa). The objective of this study is to identify potential lead biomarker candidates for response to O + C in the setting of a multi-institutional phase II study of O with and without C in recurrent platinum-sensitive OvCa. A self-selected group of patients participated in a prospectively planned exploratory biomarker substudy of the randomized phase II study of O versus O + C. Whole blood for peripheral blood mononuclear cell (PBMC) and plasma isolation was collected prior to and on day 3 of treatment. Quantitation of circulating endothelial cells (CEC), IL-6, IL-8, VEGF, and soluble VEGFR-2 plasma concentrations, and polyADPribose (PAR) incorporation were performed. Single nucleotide polymorphism analysis of XRCC1 280H, R194W, and Q399R was done. Dynamic contrast-enhanced-magnetic resonance imaging (DCE-MRI) was performed at baseline and day 3 of treatment. Parameter changes were compared between the two arms using an exact Wilcoxon rank sum test. Kaplan-Meier and log-rank tests were used to examine survival outcome. Thirteen patients elected to participate in the translational substudy, seven patients on O and six patients on O + C. Patients on O + C had a greater decrease in IL-8 concentration and larger CEC fold increase compared with those on O alone (p = 0.026, p = 0.032). The fold increase in CEC on day 3 was associated with duration of progression-free survival (PFS) (R (2) = 0.77, 95% CI 0.55-0.97, p < 0.001). IL-8 post-pretreatment changes correlate with PFS (p = 0.028). XRCC1 DNA polymorphisms were not related to PFS. All patients had reduction in PAR incorporation, and all except one had reduction in vascular flow on DCE-MRI. Our exploratory correlative studies indicate that CEC and IL-8 changes may be

  15. Prognostic factors in primary adenocarcinoma of the small intestine: 13-year single institution experience

    Directory of Open Access Journals (Sweden)

    Jacobs Michael J

    2008-01-01

    Full Text Available Abstract Background Adenocarcinoma of the small bowel is a relatively rare malignancy as compared to the other malignancies of the gastrointestinal tract. Nonspecific presentation and infrequent occurrence often leads to a delay in diagnosis and consequent poor prognosis. Various other factors are of prognostic importance while managing these tumors. Methods The medical records of a total of 27 patients treated for adenocarcinoma of the small bowel at Providence Hospital and Medical Centers from year 1990 through 2003 were reviewed retrospectively. Data were analyzed using SPSS software (version 10.0; SPSS, Inc., Chicago, IL. Survival analyses were calculated using the Kaplan Meier method with the log rank test to assess the statistical significance. The socio-demographics (age, gender were calculated using frequency analyses. Results The patients included nine males and eighteen females with a median age at diagnosis of 62 years. Only 48% of the patients had an accurate preoperative diagnosis while another 33% had a diagnosis suspicious of small bowel malignancy. None of the patients presented in stage 1. The cumulative five-year survival was 30% while the median survival was 3.3 years. There was no 30-day mortality in the postoperative period in our series. Conclusion The univariate analysis demonstrated that tumor grade, stage at presentation, lymph nodal metastasis and resection margins were significant predictors of survival.

  16. Combined 3 Tesla MRI Biomarkers Improve the Differentiation between Benign vs Malignant Single Ring Enhancing Brain Masses.

    Directory of Open Access Journals (Sweden)

    Simone Salice

    Full Text Available To evaluate whether the combination of imaging biomarkers obtained by means of different 3 Tesla (3T Magnetic Resonance Imaging (MRI advanced techniques can improve the diagnostic accuracy in the differentiation between benign and malignant single ring-enhancing brain masses.14 patients presenting at conventional 3T MRI single brain mass with similar appearance as regard ring enhancement, presence of peri-lesional edema and absence of hemorrhage signs were included in the study. All lesions were histologically proven: 5 pyogenic abscesses, 6 glioblastomas, and 3 metastases. MRI was performed at 3 Tesla and included Diffusion Weighted Imaging (DWI, Dynamic Susceptibility Contrast -Perfusion Weighted Imaging (DSC-PWI, Magnetic Resonance Spectroscopy (MRS, and Diffusion Tensor Imaging (DTI. Imaging biomarkers derived by those advanced techniques [Cerebral Blood Flow (CBF, relative Cerebral Blood Volume (rCBV, relative Main Transit Time (rMTT, Choline (Cho, Creatine (Cr, Succinate, N-Acetyl Aspartate (NAA, Lactate (Lac, Lipids, relative Apparent Diffusion Coefficient (rADC, and Fractional Anisotropy (FA] were detected by two experienced neuroradiologists in joint session in 4 areas: Internal Cavity (IC, Ring Enhancement (RE, Peri-Lesional edema (PL, and Contralateral Normal Appearing White Matter (CNAWM. Significant differences between benign (n = 5 and malignant (n = 9 ring enhancing lesions were tested with Mann-Withney U test. The diagnostic accuracy of MRI biomarkers taken alone and MRI biomarkers ratios were tested with Receiver Operating Characteristic (ROC analysis with an Area Under the Curve (AUC ≥ 0.9 indicating a very good diagnostic accuracy of the variable.Five MRI biomarker ratios achieved excellent accuracy: IC-rADC/PL-NAA (AUC = 1, IC-rADC/IC-FA (AUC = 0.978, RE-rCBV/RE-FA (AUC = 0.933, IC-rADC/RE-FA (AUC = 0.911, and IC-rADC/PL-FA (AUC = 0.911. Only IC-rADC achieved a very good diagnostic accuracy (AUC = 0.909 among MRI biomarkers

  17. Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers

    DEFF Research Database (Denmark)

    Pedersen, Mette Ølgod; Gang, Anne Ortved; Brown, Peter

    2017-01-01

    BACKGROUND: Double expression of MYC and BCL2 proteins (DE) and double-hit MYC+BCL2/BCL6 translocations (DH) were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) by the 2016 revision of the World Health Organization classification of lymphoid neoplasms...... in situ hybridization (FISH). RESULTS: DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS) in patients treated with R-CHOP but not R-CHOEP (peffect of DE for response (PFS) to R...

  18. Quantitative Analysis of "1"8F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Cui, Yi; Song, Jie; Pollom, Erqi; Alagappan, Muthuraman; Shirato, Hiroki; Chang, Daniel T.; Koong, Albert C.; Li, Ruijiang

    2016-01-01

    Purpose: To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. Methods and Materials: In this institutional review board–approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT "1"8F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162 robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. Results: The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6

  19. Analysis of PI3K/mTOR Pathway Biomarkers and Their Prognostic Value in Women with Hormone Receptor–Positive, HER2-Negative Early Breast Cancer

    Directory of Open Access Journals (Sweden)

    Hamdy A. Azim

    2016-04-01

    .6%, respectively. PIK3CA mutations were found in 7 patients (29.2%. PI3K mutations were correlated with nuclear localization of pAKT (i.e., decreased cytoplasmic pAKT, P = .04; and increased nuclear pAKT, P = .10. There was a tendency toward an inverse correlation between PI3K mutations and the expression of pS6RP (P = .10 and p4EBP1 (P = .19. Nuclear LKB1 expression was a marker of good prognosis. It was associated with smaller tumors (P = .05, more ER (P = .08 and progesteron receptor (PgR positivity (P = .002. In the Kaplan Meier (KM model, patients with high nuclear LKB1 had longer DFS (hazard ratio = 0.36; 95% confidence interval, 0.15-1.10; P = .08. Nuclear pAKT high expression also carried a tendency toward longer DFS (hazard ratio = 0.51; 95% confidence interval, 0.11-1.16; P = .13. The expression of p4EBP1, pS6RP, and the PI3K mutational status did not show any prognostic significance in our cohort. CONCLUSION: Among the studied biomarkers, only nuclear expression of LKB1 and pAKT tended to predict better survival in breast cancer patients. PI3K mutation was correlated with the expression of nuclear pAKT but not pS6RP or p4EBP1.

  20. Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and an electrochemiluminescense-based multi-array platform.

    Directory of Open Access Journals (Sweden)

    Bas C T van Bussel

    Full Text Available BACKGROUND: In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. METHODS: We measured, in a large ongoing cohort study (n = 574, by means of both a 4-plex multi-array biomarker assay developed by MesoScaleDiscovery (MSD and single-biomarker techniques (ELISA or immunoturbidimetric assay, the following biomarkers of low-grade inflammation: C-reactive protein (CRP, serum amyloid A (SAA, soluble intercellular adhesion molecule 1 (sICAM-1 and soluble vascular cell adhesion molecule 1 (sVCAM-1. These measures were realigned by weighted Deming regression and compared across a wide spectrum of subjects' cardiovascular risk factors by ANOVA. RESULTS: Despite that both methods ranked individuals' levels of biomarkers very similarly (Pearson's r all≥0.755 absolute concentrations of all biomarkers differed significantly between methods. Equations retrieved by the Deming regression enabled proper realignment of the data to overcome these differences, such that intra-class correlation coefficients were then 0.996 (CRP, 0.711 (SAA, 0.895 (sICAM-1 and 0.858 (sVCAM-1. Additionally, individual biomarkers differed across categories of glucose metabolism, weight, metabolic syndrome and smoking status to a similar extent by either method. CONCLUSIONS: Multiple low-grade inflammatory biomarker data obtained by the 4-plex multi-array platform of MSD or by well-established single-biomarker methods are comparable after proper realignment of differences in absolute concentrations, and are equally associated with cardiovascular risk factors, regardless of such differences. Given its greater efficiency, the MSD platform is a potential tool for the quantification of multiple biomarkers of low-grade inflammation in large ongoing and future clinical studies.

  1. Biomarkers of adverse drug reactions.

    Science.gov (United States)

    Carr, Daniel F; Pirmohamed, Munir

    2018-02-01

    Adverse drug reactions can be caused by a wide range of therapeutics. Adverse drug reactions affect many bodily organ systems and vary widely in severity. Milder adverse drug reactions often resolve quickly following withdrawal of the casual drug or sometimes after dose reduction. Some adverse drug reactions are severe and lead to significant organ/tissue injury which can be fatal. Adverse drug reactions also represent a financial burden to both healthcare providers and the pharmaceutical industry. Thus, a number of stakeholders would benefit from development of new, robust biomarkers for the prediction, diagnosis, and prognostication of adverse drug reactions. There has been significant recent progress in identifying predictive genomic biomarkers with the potential to be used in clinical settings to reduce the burden of adverse drug reactions. These have included biomarkers that can be used to alter drug dose (for example, Thiopurine methyltransferase (TPMT) and azathioprine dose) and drug choice. The latter have in particular included human leukocyte antigen (HLA) biomarkers which identify susceptibility to immune-mediated injuries to major organs such as skin, liver, and bone marrow from a variety of drugs. This review covers both the current state of the art with regard to genomic adverse drug reaction biomarkers. We also review circulating biomarkers that have the potential to be used for both diagnosis and prognosis, and have the added advantage of providing mechanistic information. In the future, we will not be relying on single biomarkers (genomic/non-genomic), but on multiple biomarker panels, integrated through the application of different omics technologies, which will provide information on predisposition, early diagnosis, prognosis, and mechanisms. Impact statement • Genetic and circulating biomarkers present significant opportunities to personalize patient therapy to minimize the risk of adverse drug reactions. ADRs are a significant heath issue

  2. Neurological prognostication of outcome in patients in coma after cardiac arrest.

    Science.gov (United States)

    Rossetti, Andrea O; Rabinstein, Alejandro A; Oddo, Mauro

    2016-05-01

    Management of coma after cardiac arrest has improved during the past decade, allowing an increasing proportion of patients to survive, thus prognostication has become an integral part of post-resuscitation care. Neurologists are increasingly confronted with raised expectations of next of kin and the necessity to provide early predictions of long-term prognosis. During the past decade, as technology and clinical evidence have evolved, post-cardiac arrest prognostication has moved towards a multimodal paradigm combining clinical examination with additional methods, consisting of electrophysiology, blood biomarkers, and brain imaging, to optimise prognostic accuracy. Prognostication should never be based on a single indicator; although some variables have very low false positive rates for poor outcome, multimodal assessment provides resassurance about the reliability of a prognostic estimate by offering concordant evidence. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Single nucleotide polymorphisms as susceptibility, prognostic, and therapeutic markers of nonsmall cell lung cancer

    Directory of Open Access Journals (Sweden)

    Zienolddiny S

    2011-12-01

    Full Text Available Shanbeh Zienolddiny, Vidar SkaugSection for Toxicology and Biological Work Environment, National Institute of Occupational Health, Oslo, NorwayAbstract: Lung cancer is a major public health problem throughout the world. Among the most frequent cancer types (prostate, breast, colorectal, stomach, lung, lung cancer is the leading cause of cancer-related deaths worldwide. Among the two major subtypes of small cell lung cancer and nonsmall cell lung cancer (NSCLC, 85% of tumors belong to the NSCLC histological types. Small cell lung cancer is associated with the shortest survival time. Although tobacco smoking has been recognized as the major risk factor for lung cancer, there is a great interindividual and interethnic difference in risk of developing lung cancer given exposure to similar environmental and lifestyle factors. This may indicate that in addition to chemical and environmental factors, genetic variations in the genome may contribute to risk modification. A common type of genetic variation in the genome, known as single nucleotide polymorphism, has been found to be associated with susceptibility to lung cancer. Interestingly, many of these polymorphisms are found in the genes that regulate major pathways of carcinogen metabolism (cytochrome P450 genes, detoxification (glutathione S-transferases, adduct removal (DNA repair genes, cell growth/apoptosis (TP53/MDM2, the immune system (cytokines/chemokines, and membrane receptors (nicotinic acetylcholine and dopaminergic receptors. Some of these polymorphisms have been shown to alter the level of mRNA, and protein structure and function. In addition to being susceptibility markers, several of these polymorphisms are emerging to be important for response to chemotherapy/radiotherapy and survival of patients. Therefore, it is hypothesized that single nucleotide polymorphisms will be valuable genetic markers in individual-based prognosis and therapy in future. Here we will review some of the most

  4. Prognostic value of trisomy 8 as a single anomaly and the influence of additional cytogenetic aberrations in primary myelodysplastic syndromes.

    Science.gov (United States)

    Saumell, Sílvia; Florensa, Lourdes; Luño, Elisa; Sanzo, Carmen; Cañizo, Consuelo; Hernández, Jesus M; Cervera, José; Gallart, Miguel A; Carbonell, Félix; Collado, Rosa; Arenillas, Leonor; Pedro, Carme; Bargay, Joan; Nomdedeu, Benet; Xicoy, Blanca; Vallespí, Teresa; Raya, José M; Belloch, Luis; Sanz, Guillermo F; Solé, Francesc

    2012-11-01

    Trisomy 8 is the most common chromosomal gain in myelodysplastic syndromes (MDS), however, little is known about the features of MDS with isolated trisomy 8 and the influence of additional cytogenetic aberrations. We determined the characteristics and prognostic factors of 72 patients with trisomy 8 as a single anomaly and analysed also the impact of other aberrations added to trisomy 8 in another 62 patients. According to our study, MDS with isolated trisomy 8 was more frequent in men, with more than one cytopenia in most patients (62%) and having about 4% bone marrow blasts. The multivariate analysis demonstrated that platelet count and percentage bone marrow blasts had the strongest impact on overall survival (OS). The median OS for isolated trisomy 8, trisomy 8 plus one aberration (tr8 + 1), plus two (tr8 + 2) and plus three or more aberrations (tr8 + ≥3) was 34·3, 40, 23·4 and 5·8 months, respectively (P < 0·001). Trisomy 8 confers a poorer prognosis than a normal karyotype in MDS patients with ≥5% bone marrow blasts. This study supports the view that MDS with isolated trisomy 8 should be included in the intermediate cytogenetic risk group. © 2012 Blackwell Publishing Ltd.

  5. Prognostic Utility of Stress Testing and Cardiac Biomarkers in Menopausal Women at Low to Intermediate Risk for Coronary ARTery Disease (SMART Study): 5-Year Outcome.

    Science.gov (United States)

    Abdelmoneim, Sahar S; Ball, Caroline A; Mantovani, Francesca; Hagen, Mary E; Eifert-Rain, Susan; Wilansky, Susan; Castello, Ramon; Pellikka, Patricia A; Best, Patricia J M; Mulvagh, Sharon L

    2018-05-01

    In women with low to intermediate risk of coronary artery disease (CAD), prognostic detection strategies have been controversial. We present the follow-up data of the SMART trial in peri/postmenopausal women at low to intermediate risk of CAD. To determine the value of contrast stress echocardiography (CSE), stress electrocardiogram (sECG), and serum biomarkers for prediction of cardiovascular events (CE) in peri/postmenopausal women at low to intermediate risk of CAD. From January 2004 to August 2007, 400 peri/postmenopausal women were prospectively enrolled. All women had detailed risk factor assessment, and underwent simultaneous CSE (Definity ® , Lantheus Medical Imaging) and sECG. Laboratories included brain natriuretic peptide (BNP), atrial natriuretic peptide, endothelin, and high sensitivity C-reactive protein. Wall motion score index was based on a 16-segment model. Abnormal CSE was defined as new or worsening wall motion abnormality at stress, while abnormal sECG was ≥1 mm horizontal/downsloping ST segment depression/elevation (80 mseconds duration). Self-reported outcome data were collected from a mailed Women's Heart Clinic Questionnaire. CE outcomes included all-cause mortality, nonfatal myocardial infarction (MI), heart failure, chest pain hospitalization or development of typical angina (CP), and revascularization (REVASC). Adjusted Cox proportional hazard ratios (HR; 95% confidence intervals) were reported. A total of 366 women (54.4 ± 5.5 years, Framingham risk 6.5% ± 4.4%) completed simultaneous CSE and sECG. Forty-two (11.5%) had abnormal CSE, while sECG was abnormal in 22 (6%) women. Follow-up (4.4 ± 1.2 years) was available in 315/366 (86%) women (78% exercise-CSE, 22% dobutamine-CSE). In those who completed follow-up, CSE was abnormal in 33 women (10.5%) and sECG was abnormal in 21 (6.7%). In 33 women with abnormal CSE, sECG was abnormal in 7 (21.2%) and normal in 26 (79%), p = 0.0004. CE occurred in 27 (8.6%) women: 8

  6. Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers.

    Directory of Open Access Journals (Sweden)

    Mette Ølgod Pedersen

    Full Text Available Double expression of MYC and BCL2 proteins (DE and double-hit MYC+BCL2/BCL6 translocations (DH were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL by the 2016 revision of the World Health Organization classification of lymphoid neoplasms. Whether this applies to the subgroup of young patients with high risk DLBCL is not known. We previously found that in a uniform retrospective population-based cohort of patients aged 18-60 years with high-risk DLBCL, the addition of etoposide to R-CHOP chemotherapy (R-CHOEP resulted in improved survival mainly in patients with germinal center B-cell like (GCB immunophenotype. The aim of this study was to investigate the prognostic and predictive value of DE and DH in this patient cohort.Data on all young Danish patients diagnosed with de novo high-risk DLBCL 2004-2008 and treated with R-CHOP or R-CHOEP were obtained from the Danish Lymphoma database (n = 159. Tumor samples were available from 103 patients. MYC and BCL2 proteins were analyzed with quantitative immunohistochemistry (IHC using different cut off values. MYC-, BCL2- and BCL6-translocations were examined with fluorescent in situ hybridization (FISH.DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS in patients treated with R-CHOP but not R-CHOEP (p<0.001, also after exclusion of patients with DH. A predictive effect of DE for response (PFS to R-CHOEP vs. R-CHOP was almost significant (p = 0.07. DH was not prognostic in this patient cohort.In young patients with high-risk DLBCL, treatment with R-CHOEP may overcome the negative prognostic impact of DE observed in patients treated with R-CHOP.

  7. Single and multiple cardiovascular biomarkers in subjects without a previous cardiovascular event

    DEFF Research Database (Denmark)

    Pareek, Manan; Bhatt, Deepak L; Vaduganathan, Muthiah

    2017-01-01

    Aims To assess the incremental value of biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and procollagen type 1...

  8. The Prognostic Role of Magnetic Resonance Imaging and Single-Photon Emission Computed Tomography in Viral Encephalitis

    Energy Technology Data Exchange (ETDEWEB)

    Misra, U.K.; Kalita, J.; Srivastav, A.; Pradhan, P.K. (Depts. of Neurology and Nuclear Medicine, Sanjay Gandhi Post Graduate Inst. of Medical Sciences, Lucknow (India))

    2008-09-15

    Background: There is a paucity of studies evaluating the prognostic role of magnetic resonance imaging (MRI) and single-photon emission computed tomography (SPECT) changes in viral encephalitis. Purpose: To study MRI and SPECT changes in patients with viral encephalitis, and to correlate these changes with clinical findings and outcome. Material and Methods: During 1997-2006, 31 encephalitis patients (aged 2-60 years; nine females, 22 males) underwent both MRI and SPECT studies. Their demographic and clinical data and 6-month outcome were recorded. For the diagnosis of encephalitis, polymerase chain reaction (PCR) and IgM enzyme-linked immunosorbent assay (ELISA) were carried out. Cranial MRI was done on a 1.5 T scanner, and 99mTc ethylene cysteine dimer (ECD) SPECT using a gamma camera. Outcome was defined at 6 months as complete, partial, or poor recovery. Results: 19 patients had Japanese encephalitis (JE), one had herpes simplex encephalitis (HSE), and 11 had nonspecific encephalitis. Movement disorders were present in 21, parkinsonian features in 19, and dystonia in 16 patients. MRI was abnormal in 20 patients, and revealed thalamic involvement in 17, basal ganglia in eight, brainstem in 11, and cortical in two. SPECT revealed hypoperfusion in 22 patients, which was cortical in 11, thalamic in 10, basal ganglia in six, and midbrain in one. Cortical involvement was more frequently found by SPECT and brainstem involvement by MRI. Outcome of encephalitis did not differ in the different groups of encephalitis and MRI changes. Conclusion: MRI and SPECT show a spectrum of findings in encephalitis, but these do not correlate with 6-month outcome

  9. Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy

    DEFF Research Database (Denmark)

    Templeton, Arnoud J; Knox, Jennifer J; Lin, Xun

    2016-01-01

    at baseline and 6 (± 2) wk later. A landmark analysis at 8 wk was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate using Cox or logistic regression models, adjusted for variables in IMDC score and NLR values...

  10. Prognostic relevance of human papillomavirus L1 capsid protein detection within mild and moderate dysplastic lesions of the cervix uteri in combination with p16 biomarker

    DEFF Research Database (Denmark)

    Hilfrich, Ralf; Hariri, Jalil

    2008-01-01

    OBJECTIVE: To proof the prognostic relevance of HPV L1 capsid protein detection on colposcopically-guided punch biopsies in combination with p16. STUDY DESIGN: Sections of colposcopically-guided punch biopsies from 191 consecutive cases with at least 5 years of follow-up were stained with HPV L1 ...

  11. Pleural effusion biomarkers and computed tomography findings in diagnosing malignant pleural mesothelioma: A retrospective study in a single center

    Science.gov (United States)

    Kataoka, Yuki; Ikegaki, Shunkichi; Saito, Emiko; Matsumoto, Hirotaka; Kaku, Sawako; Shimada, Masatoshi; Hirabayashi, Masataka

    2017-01-01

    In this study, we aimed to examine the clinical value of the pleural effusion (PE) biomarkers, soluble mesothelin-related peptide (SMRP), cytokeratin 19 fragment (CYFRA 21–1) and carcinoembryonic antigen (CEA), and the utility of combining chest computed tomography (CT) findings with these biomarkers, in diagnosing malignant pleural mesothelioma (MPM). We conducted a retrospective cohort study in a single center. Consecutive patients with undiagnosed pleural effusions who underwent PE analysis between September 2014 and August 2016 were reviewed. This study included 240 patients (32 with MPM and 208 non-MPM). SMRP and the CYFRA 21-1/CEA ratio had a sensitivity and specificity for diagnosing MPM of 56.3% and 86.5%, and 87.5% and 74.0%, respectively. Using receiver operating characteristics (ROC) curve analysis of the ability of these markers to distinguish MPM from all other PE causes, the area under the ROC curve (AUC) for SMRP and the CYFRA 21-1/CEA ratio was 0.804 and 0.874, respectively. The sensitivity and specificity of SMRP combined with the CYFRA 21-1/CEA ratio were 93.8% and 64.9%, respectively. The sensitivity of the combination of SMRP, the CYFRA 21-1/CEA ratio, and the presence of Leung’s criteria (a chest CT finding that is suggestive of malignant pleural disease) was 93.8%. In conclusion, the combined PE biomarkers had a high sensitivity for diagnosing MPM, although the addition of chest CT findings did not improve the sensitivity of SMRP combined with the CYFRA 21-1/CEA ratio. Combination of these biomarkers helped to rule out MPM effectively among patients at high risk of suffering MPM and would be valuable especially for old frail patients who have difficulty in undergoing invasive procedures such as thoracoscopy. PMID:28968445

  12. Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

    International Nuclear Information System (INIS)

    Harima, Yoko; Ikeda, Koshi; Utsunomiya, Keita; Komemushi, Atsushi; Kanno, Shohei; Shiga, Toshiko; Tanigawa, Noboru

    2013-01-01

    Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC

  13. Apolipoprotein C-II Is a Potential Serum Biomarker as a Prognostic Factor of Locally Advanced Cervical Cancer After Chemoradiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Harima, Yoko, E-mail: harima@takii.kmu.ac.jp [Department of Radiology, Takii Hospital, Kansai Medical University, Moriguchi, Osaka (Japan); Ikeda, Koshi; Utsunomiya, Keita; Komemushi, Atsushi; Kanno, Shohei; Shiga, Toshiko [Department of Radiology, Takii Hospital, Kansai Medical University, Moriguchi, Osaka (Japan); Tanigawa, Noboru [Department of Radiology, Hirakata Hospital, Kansai Medical University, Hirakata, Osaka (Japan)

    2013-12-01

    Purpose: To determine pretreatment serum protein levels for generally applicable measurement to predict chemoradiation treatment outcomes in patients with locally advanced squamous cell cervical carcinoma (CC). Methods and Materials: In a screening study, measurements were conducted twice. At first, 6 serum samples from CC patients (3 with no evidence of disease [NED] and 3 with cancer-caused death [CD]) and 2 from healthy controls were tested. Next, 12 serum samples from different CC patients (8 NED, 4 CD) and 4 from healthy controls were examined. Subsequently, 28 different CC patients (18 NED, 10 CD) and 9 controls were analyzed in the validation study. Protein chips were treated with the sample sera, and the serum protein pattern was detected by surface-enhanced laser desorption and ionization–time-of-flight mass spectrometry (SELDI-TOF MS). Then, single MS-based peptide mass fingerprinting (PMF) and tandem MS (MS/MS)-based peptide/protein identification methods, were used to identify protein corresponding to the detected peak. And then, turbidimetric assay was used to measure the levels of a protein that indicated the best match with this peptide peak. Results: The same peak 8918 m/z was identified in both screening studies. Neither the screening study nor the validation study had significant differences in the appearance of this peak in the controls and NED. However, the intensity of the peak in CD was significantly lower than that of controls and NED in both pilot studies (P=.02, P=.04) and validation study (P=.01, P=.001). The protein indicated the best match with this peptide peak at 8918 m/z was identified as apolipoprotein C-II (ApoC-II) using PMF and MS/MS methods. Turbidimetric assay showed that the mean serum levels of ApoC-II tended to decrease in CD group when compared with NED group (P=.078). Conclusion: ApoC-II could be used as a biomarker for detection in predicting and estimating the radiation treatment outcome of patients with CC.

  14. Prognostic factors and long-term outcomes of hilar cholangiocarcinoma: A single-institution experience in China

    Science.gov (United States)

    Hu, Hai-Jie; Mao, Hui; Shrestha, Anuj; Tan, Yong-Qiong; Ma, Wen-Jie; Yang, Qin; Wang, Jun-Ke; Cheng, Nan-Sheng; Li, Fu-Yu

    2016-01-01

    AIM: To evaluate the prognostic factors of hilar cholangiocarcinoma in a large series of patients in a single institution. METHODS: Eight hundred and fourteen patients with a diagnosis of hilar cholangiocarcinoma that were evaluated and treated between 1990 and 2014, of which 381 patients underwent curative surgery, were included in this study. Potential factors associated with overall survival (OS) and disease-free survival (DFS) were evaluated by univariate and multivariate analyses. RESULTS: Curative surgery provided the best long-term survival with a median OS of 26.3 mo. The median DFS was 18.1 mo. Multivariate analysis showed that patients with tumor size > 3 cm [hazard ratio (HR) = 1.482, 95%CI: 1.127-1.949; P = 0.005], positive nodal disease (HR = 1.701, 95%CI: 1.346-2.149; P < 0.001), poor differentiation (HR = 2.535, 95%CI: 1.839-3.493; P < 0.001), vascular invasion (HR = 1.542, 95%CI: 1.082-2.197; P = 0.017), and positive margins (HR = 1.798, 95%CI: 1.314-2.461; P < 0.001) had poor OS outcome. The independent factors for DFS were positive nodal disease (HR = 3.383, 95%CI: 2.633-4.348; P < 0.001), poor differentiation (HR = 2.774, 95%CI: 2.012-3.823; P < 0.001), vascular invasion (HR = 2.136, 95%CI: 1.658-3.236; P < 0.001), and positive margins (HR = 1.835, 95%CI: 1.256-2.679; P < 0.001). Multiple logistic regression analysis showed that caudate lobectomy [odds ratio (OR) = 9.771, 95%CI: 4.672-20.433; P < 0.001], tumor diameter (OR = 3.772, 95%CI: 1.914-7.434; P < 0.001), surgical procedures (OR = 10.236, 95%CI: 4.738-22.116; P < 0.001), American Joint Committee On Cancer T stage (OR = 2.010, 95%CI: 1.043-3.870; P = 0.037), and vascular invasion (OR = 2.278, 95%CI: 0.997-5.207; P = 0.051) were independently associated with tumor-free margin, and surgical procedures could indirectly affect survival outcome by influencing the tumor resection margin. CONCLUSION: Tumor margin, tumor differentiation, vascular invasion, and lymph node status were independent

  15. Indistinguishable genomic profiles and shared prognostic markers in undifferentiated pleomorphic sarcoma and leiomyosarcoma: different sides of a single coin?

    DEFF Research Database (Denmark)

    Carneiro, Ana; Francis, Princy; Bendahl, Pär-Ola

    2009-01-01

    Soft tissue sarcoma (STS) diagnostics and prognostics are challenging, particularly in highly malignant and pleomorphic subtypes such as undifferentiated pleomorphic sarcoma (UPS) and leiomyosarcoma (LMS). We applied 32K BAC arrays and gene expression profiling to 18 extremity soft tissue LMS and...

  16. Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging biomarker in cervical cancer patients treated with definitive chemoradiation

    International Nuclear Information System (INIS)

    Marconi, Daniel Grossi; Fregnani, Jose Humberto Tavares Guerreiro; Rossini, Rodrigo Ribeiro; Netto, Ana Karina Borges Junqueira; Lucchesi, Fabiano Rubião; Tsunoda, Audrey Tieko; Kamrava, Mitchell

    2016-01-01

    Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) has been studed in several cancers including cervical cancer. This study was designed to investigate the association of DW-MRI parameters with baseline clinical features and clinical outcomes (local regional control (LRC), disease free survival (DFS) and disease specific survival (DSS)) in cervical cancer patients treated with definitive chemoradiation. This was a retrospective study approved by an institutional review board that included 66 women with cervical cancer treated with definitive chemoradiation who underwent pre-treatment MRI at our institution between 2012 and 2013. A region of interest (ROI) was manually drawn by one of three radiologists with experience in pelvic imaging on a single axial CT slice encompassing the widest diameter of the cervical tumor while excluding areas of necrosis. The following apparent diffusion coefficient (ADC) values (×10 −3 mm 2 /s) were extracted for each ROI: Minimum - ADC min , Maximum - ADC max , Mean - ADC mean , and Standard Deviation of the ADC - ADC dev . Receiver operating characteristic (ROC) curves were built to choose the most accurate cut off value for each ADC value. Correlation between imaging metrics and baseline clinical features were evaluated using the Mann Whitney test. Confirmatory multi-variate Cox modeling was used to test associations with LRC (adjusted by gross tumor volume – GTV), DFS and DSS (both adjusted by FIGO stage). Kaplan Meyer curves were built for DFS and DSS. A p-value < 0.05 was considered significant. Women median age was 52 years (range 23–90). 67 % had FIGO stage I-II disease while 33 % had FIGO stage III-IV disease. Eighty-two percent had squamous cell cancer. Eighty-eight percent received concurrent cisplatin chemotherapy with radiation. Median EQD2 of external beam and brachytherapy was 82.2 Gy (range 74–84). Women with disease staged III-IV (FIGO) had significantly higher mean ADC max values compared with those

  17. Multiple inflammatory biomarker detection in a prospective cohort study: a cross-validation between well-established single-biomarker techniques and electrochemiluminescense-based multi-array platform

    NARCIS (Netherlands)

    Bussel, van B.C.T.; Ferreira, I.; Waarenburg, M.P.H.; Greevenbroek, van M.M.J.; Kallen, van der C.J.H.; Henry, R.M.A.; Feskens, E.J.M.; Stehouwer, C.D.A.; Schalkwijk, C.G.

    2013-01-01

    Background - In terms of time, effort and quality, multiplex technology is an attractive alternative for well-established single-biomarker measurements in clinical studies. However, limited data comparing these methods are available. Methods - We measured, in a large ongoing cohort study (n = 574),

  18. NKp46 expression on NK cells as a prognostic and predictive biomarker for response to allo-SCT in patients with AML.

    Science.gov (United States)

    Chretien, Anne-Sophie; Devillier, Raynier; Fauriat, Cyril; Orlanducci, Florence; Harbi, Samia; Le Roy, Aude; Rey, Jérôme; Bouvier Borg, Gaelle; Gautherot, Emmanuel; Hamel, Jean-François; Ifrah, Norbert; Lacombe, Catherine; Cornillet-Lefebvre, Pascale; Delaunay, Jacques; Toubert, Antoine; Arnoulet, Christine; Vey, Norbert; Blaise, Didier; Olive, Daniel

    2017-01-01

    NKp46 is a major determinant of natural killer (NK) cell function and it is implicated in tumor immune surveillance in acute myeloid leukemia (AML). The purpose of this study was to investigate the prognostic significance of NKp46 expression in an independent cohort of patients with AML, and to investigate the impact of NKp46 on clinical outcome after allogeneic stem cell transplantation (allo-SCT). NKp46 expression was assessed at diagnosis on NK cells by flow cytometry (N = 180 patients). Clinical outcome was evaluated with regard to NKp46 expression. Patients with NKp46 high phenotype at diagnosis had better progression-free survival (PFS) and overall survival (OS) than patients with NKp46 low phenotype (74.3% vs. 46.6%, p = 0.014; 82.6% vs. 57.1%, p = 0.010, respectively). In multivariate analysis, high NKp46 was an independent factor for improved OS (HR = 0.409, p = 0.010) and PFS (HR = 0.335, p = 0.011). Subgroup analysis revealed that allo-SCT had a favorable impact on PFS in patients with NKp46 high phenotype ( p = 0.025). By contrast, allo-SCT did not impact PFS in patients with low NKp46 expression ( p = 0.303). In conclusion, we validate the prognostic value of NKp46 expression at diagnosis in AML. However, the prognostic value of NKp46 expression is limited to patients treated with allo-SCT, thus suggesting that NKp46 status may be predictive for allo-SCT responsiveness.

  19. Causes and prognostic factors for early death in patients with acute promyelocytic leukemia treated with single-agent arsenic trioxide.

    Science.gov (United States)

    Hou, Jinxiao; Wang, Shuye; Zhang, Yingmei; Fan, Dachuan; Li, Haitao; Yang, Yiju; Ge, Fei; Hou, Wenyi; Fu, Jinyue; Wang, Ping; Zhao, Hongli; Sun, Jiayue; Yang, Kunpeng; Zhou, Jin; Li, Xiaoxia

    2017-12-01

    Early death (ED) is one of the most critical issues involved in the current care of patients with acute promyelocytic leukemia (APL). Factors identified as independent predictors of ED varied among published studies. We retrospectively analyzed the incidence, causes, and prognostic factors of ED in a series of 216 patients with newly diagnosed APL who received arsenic trioxide (ATO) as induction therapy. Multivariate logistic regression analysis was used to determine the association of clinical factors with overall ED, hemorrhagic ED, death within 7 days, and death within 8-30 days. In total, 35 EDs (16.2%) occurred that were caused by hemorrhage, differentiation syndrome (DS), infection, and other causes, in order of prevalence. The independent prognostic factors for overall ED and death within 8-30 days were the same and included serum creatinine level, Eastern Cooperative Oncology Group (ECOG) score, sex, and fibrinogen level. The risk factors for hemorrhagic ED and death within 7 days were similar and included serum creatinine level, ECOG score, and white blood cell count, while hemorrhagic ED was also associated with D-dimer. Our findings revealed a high rate of ED, and the causes of ED were similar to those among patients who received ATRA-based therapy. Increased creatinine level was the most powerful predictor, and an ECOG score greater than 2 was another strong prognostic factor for all four types of ED.

  20. Bayesian additive decision trees of biomarker by treatment interactions for predictive biomarker detection and subgroup identification.

    Science.gov (United States)

    Zhao, Yang; Zheng, Wei; Zhuo, Daisy Y; Lu, Yuefeng; Ma, Xiwen; Liu, Hengchang; Zeng, Zhen; Laird, Glen

    2017-10-11

    Personalized medicine, or tailored therapy, has been an active and important topic in recent medical research. Many methods have been proposed in the literature for predictive biomarker detection and subgroup identification. In this article, we propose a novel decision tree-based approach applicable in randomized clinical trials. We model the prognostic effects of the biomarkers using additive regression trees and the biomarker-by-treatment effect using a single regression tree. Bayesian approach is utilized to periodically revise the split variables and the split rules of the decision trees, which provides a better overall fitting. Gibbs sampler is implemented in the MCMC procedure, which updates the prognostic trees and the interaction tree separately. We use the posterior distribution of the interaction tree to construct the predictive scores of the biomarkers and to identify the subgroup where the treatment is superior to the control. Numerical simulations show that our proposed method performs well under various settings comparing to existing methods. We also demonstrate an application of our method in a real clinical trial.

  1. Prognostic factors for survival in patients with colorectal liver metastases: experience of a single brazilian cancer center

    Directory of Open Access Journals (Sweden)

    Héber Salvador de Castro Ribeiro

    2012-12-01

    Full Text Available CONTEXT: Liver metastases are a common event in the clinical outcome of patients with colorectal cancer and account for 2/3 of deaths from this disease. There is considerable controversy among the data in the literature regarding the results of surgical treatment and prognostic factors of survival, and no analysis have been done in a large cohort of patients in Brazil. OBJECTIVES: To characterize the results of surgical treatment of patients with colorectal liver metastases, and to establish prognostic factors of survival in a Brazilian population. METHOD: This was a retrospective study of patients undergoing liver resection for colorectal metastases in a tertiary cancer hospital from 1998 to 2009. We analyzed epidemiologic variables and the clinical characteristics of primary tumors, metastatic disease and its treatment, surgical procedures and follow-up, and survival results. Survival analyzes were done by the Kaplan-Meier method and the log-rank test was applied to determine the influence of variables on overall and disease-free survival. All variables associated with survival with P<0.20 in univariate analysis, were included in multivariate analysis using a Cox proportional hazard regression model. RESULTS: During the period analyzed, 209 procedures were performed on 170 patients. Postope-rative mortality in 90 days was 2.9% and 5-year overall survival was 64.9%. Its independent prognostic factors were the presence of extrahepatic disease at diagnosis of liver metastases, bilateral nodules and the occurrence of major complications after liver surgery. The estimated 5-year disease-free survival was 39.1% and its prognostic factors included R1 resection, extrahepatic disease, bilateral nodules, lymph node involvement in the primary tumor and primary tumors located in the rectum. CONCLUSION: Liver resection for colorectal metastases is safe and effective and the analysis of prognostic factors of survival in a large cohort of Brazilian patients

  2. Double positivity for HPV-DNA/p16ink4a is the biomarker with strongest diagnostic accuracy and prognostic value for human papillomavirus related oropharyngeal cancer patients.

    Science.gov (United States)

    Mena, Marisa; Taberna, Miren; Tous, Sara; Marquez, Sandra; Clavero, Omar; Quiros, Beatriz; Lloveras, Belen; Alejo, Maria; Leon, Xavier; Quer, Miquel; Bagué, Silvia; Mesia, Ricard; Nogués, Julio; Gomà, Montserrat; Aguila, Anton; Bonfill, Teresa; Blazquez, Carmen; Guix, Marta; Hijano, Rafael; Torres, Montserrat; Holzinger, Dana; Pawlita, Michael; Pavon, Miguel Angel; Bravo, Ignacio G; de Sanjosé, Silvia; Bosch, Francesc Xavier; Alemany, Laia

    2018-03-01

    The etiologic role of human papillomaviruses (HPV) in oropharyngeal cancer (OPC) is well established. Nevertheless, information on survival differences by anatomic sub-site or treatment remains scarce, and it is still unclear the HPV-relatedness definition with best diagnostic accuracy and prognostic value. We conducted a retrospective cohort study of all patients diagnosed with a primary OPC in four Catalonian hospitals from 1990 to 2013. Formalin-fixed, paraffin-embedded cancer tissues were subjected to histopathological evaluation, DNA quality control, HPV-DNA detection, and p16 INK4a /pRb/p53/Cyclin-D1 immunohistochemistry. HPV-DNA positive and a random sample of HPV-DNA negative cases were subjected to HPV-E6*I mRNA detection. Demographic, tobacco/alcohol use, clinical and follow-up data were collected. Multivariate models were used to evaluate factors associated with HPV positivity as defined by four different HPV-relatedness definitions. Proportional-hazards models were used to compare the risk of death and recurrence among HPV-related and non-related OPC. 788 patients yielded a valid HPV-DNA result. The percentage of positive cases was 10.9%, 10.2%, 8.5% and 7.4% for p16 INK4a , HPV-DNA, HPV-DNA/HPV-E6*I mRNA, and HPV-DNA/p16 INK4a , respectively. Being non-smoker or non-drinker was consistently associated across HPV-relatedness definitions with HPV positivity. A suggestion of survival differences between anatomic sub-sites and treatments was observed. Double positivity for HPV-DNA/p16 INK4a showed strongest diagnostic accuracy and prognostic value. Double positivity for HPV-DNA/p16 INK4a , a test that can be easily implemented in the clinical practice, has optimal diagnostic accuracy and prognostic value. Our results have strong clinical implications for patients' classification and handling and also suggest that not all the HPV-related OPC behave similarly. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Predictive and prognostic value of circulating nucleosomes and serum biomarkers in patients with metastasized colorectal cancer undergoing Selective Internal Radiation Therapy

    International Nuclear Information System (INIS)

    Fahmueller, Yvonne Nadine; Nagel, Dorothea; Hoffmann, Ralf-Thorsten; Tatsch, Klaus; Jakobs, Tobias; Stieber, Petra; Holdenrieder, Stefan

    2012-01-01

    Selective Internal Radiation Therapy (SIRT) is a new and effective locoregional anticancer therapy for colorectal cancer patients with liver metastases. Markers for prediction of therapy response and prognosis are needed for the individual management of those patients undergoing SIRT. Blood samples were prospectively and consecutively taken from 49 colorectal cancer patients with extensive hepatic metastases before, three, six, 24 and 48 h after SIRT to analyze the concentrations of nucleosomes and further laboratory parameters, and to compare them with the response to therapy regularly determined 3 months after therapy and with overall survival. Circulating nucleosomes, cytokeratin-19 fragments (CYFRA 21-1), carcinoembryonic antigen (CEA), C-reactive protein (CRP) and various liver markers increased already 24 h after SIRT. Pretherapeutical levels of CYFRA 21-1, CEA, cancer antigen 19-9 (CA 19-9), asparate-aminotransferase (AST) and lactate dehydrogenase (LDH) as well as 24 h values of nucleosomes were significantly higher in patients suffering from disease progression (N = 35) than in non-progressive patients (N = 14). Concerning overall survival, CEA, CA 19-9, CYFRA 21-1, CRP, LDH, AST, choline esterase (CHE), gamma-glutamyl-transferase, alkaline phosphatase, and amylase (all 0 h, 24 h) and nucleosomes (24 h) were found to be prognostic relevant markers in univariate analyses. In multivariate Cox-Regression analysis, the best prognostic model was obtained for the combination of CRP and AST. When 24 h values were additionally included, nucleosomes (24 h) further improved the existing model. Panels of biochemical markers are helpful to stratify pretherapeutically colorectal cancer patients for SIR-therapy and to early estimate the response to SIR-therapy

  4. Efficacy, safety, and biomarkers of single-agent bevacizumab therapy in patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. The 16W-DCR was 42% (95% confidence interval, 27%-57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3-4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation.

  5. De Novo Identification of Biomarker Proteins Using Tandem Mass Spectrometry

    Science.gov (United States)

    Many studies have shown that biological fluids contain an important number of biomarkers associated with various pathologies. For instance, there has been extensive research to identify effective biomarkers as prognostic indicators of breast cancer. An effective approach for biom...

  6. Prognostic parameterization of cloud ice with a single category in the aerosol-climate model ECHAM(v6.3.0)-HAM(v2.3)

    Science.gov (United States)

    Dietlicher, Remo; Neubauer, David; Lohmann, Ulrike

    2018-04-01

    A new scheme for stratiform cloud microphysics has been implemented in the ECHAM6-HAM2 general circulation model. It features a widely used description of cloud water with two categories for cloud droplets and raindrops. The unique aspect of the new scheme is the break with the traditional approach to describe cloud ice analogously. Here we parameterize cloud ice by a single category that predicts bulk particle properties (P3). This method has already been applied in a regional model and most recently also in the Community Atmosphere Model 5 (CAM5). A single cloud ice category does not rely on heuristic conversion rates from one category to another. Therefore, it is conceptually easier and closer to first principles. This work shows that a single category is a viable approach to describe cloud ice in climate models. Prognostic representation of sedimentation is achieved by a nested approach for sub-stepping the cloud microphysics scheme. This yields good results in terms of accuracy and performance as compared to simulations with high temporal resolution. Furthermore, the new scheme allows for a competition between various cloud processes and is thus able to unbiasedly represent the ice formation pathway from nucleation to growth by vapor deposition and collisions to sedimentation. Specific aspects of the P3 method are evaluated. We could not produce a purely stratiform cloud where rime growth dominates growth by vapor deposition and conclude that the lack of appropriate conditions renders the prognostic parameters associated with the rime properties unnecessary. Limitations inherent in a single category are examined.

  7. An Investigation of Modifying Effects of Metallothionein Single-Nucleotide Polymorphisms on the Association between Mercury Exposure and Biomarker Levels

    Science.gov (United States)

    Wang, Yi; Goodrich, Jaclyn M.; Gillespie, Brenda; Werner, Robert; Basu, Niladri

    2012-01-01

    Background: Recent studies have suggested that several genes that mediate mercury metabolism are polymorphic in humans. Objective: We hypothesized that single-nucleotide polymorphisms (SNPs) in metallothionein (MT) genes may underlie interindividual differences in mercury biomarker levels. We studied the potential modifying effects of MT SNPs on mercury exposure–biomarker relationships. Methods: We measured total mercury in urine and hair samples of 515 dental professionals. We also surveyed occupational and personal exposures to dental amalgam and dietary fish consumption, from which daily methylmercury (MeHg) intake was estimated. Log-transformed urine and hair levels were modeled in multivariable linear regression separately against respective exposure surrogates, and the effect modification of 13 MT SNPs on exposure was investigated. Results: The mean mercury levels in urine (1.06 μg/L) and hair (0.51 μg/g) were not significantly different from the U.S. general population (0.95 μg/L and 0.47 μg/g, respectively). The mean estimated daily MeHg intake was 0.084 μg/kg/day (range, 0–0.98 μg/kg/day), with 25% of study population intakes exceeding the current U.S. Environmental Protection Agency reference dose of 0.1 μg/kg/day. Multivariate regression analysis showed that subjects with the MT1M (rs2270837) AA genotype (n = 10) or the MT2A (rs10636) CC genotype (n = 42) had lower urinary mercury levels than did those with the MT1M or MT2A GG genotype (n = 329 and 251, respectively) after controlling for exposure and potential confounders. After controlling for MeHg intake, subjects with MT1A (rs8052394) GA and GG genotypes (n = 24) or the MT1M (rs9936741) TT genotype (n = 459) had lower hair mercury levels than did subjects with MT1A AA (n = 113) or MT1M TC and CC genotypes (n = 15), respectively. Conclusion: Our findings suggest that some MT genetic polymorphisms may influence mercury biomarker concentrations at levels of exposure relevant to the general

  8. Profiling of microRNAs in tumor interstitial fluid of breast tumors – a novel resource to identify biomarkers for prognostic classification and detection of cancer

    DEFF Research Database (Denmark)

    Halvorsen, Ann Rita; Helland, Åslaug; Gromov, Pavel

    2017-01-01

    and to elucidate the cross-talk that exists among cells in a tumor microenvironment. Matched tumor interstitial fluid samples (TIF, n = 60), normal interstitial fluid samples (NIF, n = 51), corresponding tumor tissue specimens (n = 54), and serum samples (n = 27) were collected from patients with breast cancer......, and detectable microRNAs were analyzed and compared. In addition, serum data from 32 patients with breast cancer and 22 healthy controls were obtained for a validation study. To identify potential serum biomarkers of breast cancer, first the microRNA profiles of TIF and NIF samples were compared. A total of 266...... microRNAs were present at higher level in the TIF samples as compared to normal counterparts. Sixty-one of these microRNAs were present in > 75% of the serum samples and were subsequently tested in a validation set. Seven of the 61 microRNAs were associated with poor survival, while 23 were associated...

  9. Topoisomerase I as a Biomarker: Detection of Activity at the Single Molecule Level

    DEFF Research Database (Denmark)

    Proszek, Joanna; Roy, Amit; Jakobsen, Ann-Katrine

    2014-01-01

    in hTopI have been reported to result in CPT resistance. Therefore, hTOPI gene copy number, mRNA level, protein amount, and enzyme activity have been studied to explain differences in cellular response to CPT. We show that Rolling Circle Enhanced Enzyme Activity Detection (REEAD), allowing measurement...... of hTopI cleavage-religation activity at the single molecule level, may be used to detect posttranslational enzymatic differences influencing CPT response. These differences cannot be detected by analysis of hTopI gene copy number, mRNA amount, or protein amount, and only become apparent upon measuring...

  10. Prognostic value of technetium-99m-labeled single-photon emission computerized tomography in the follow-up of patients after their first myocardial revascularization surgery

    Directory of Open Access Journals (Sweden)

    Márcia Maria Sales dos Santos

    2003-01-01

    Full Text Available OBJECTIVE: To assess the prognostic value of Technetium-99m-labeled single-photon emission computerized tomography (SPECT in the follow-up of patients who had undergone their first myocardial revascularization. METHODS: We carried out a retrospective study of 280 revascularized patients undergoing myocardial scintigraphy under stress (exercise or pharmacological stress with dipyridamole and at rest according to a 2-day protocol. A set of clinical, stress electrocardiographic and scintigraphic variables was assessed. Cardiac events were classified as "major" (death, infarction, unstable angina and "any" (major event or coronary angioplasty or new myocardial revascularization surgery. RESULTS: Thirty-six major events occurred as follows: 3 deaths, 11 infarctions, and 22 unstable anginas. In regard to any event, 22 angioplasties and 7 new surgeries occurred in addition to major events, resulting a total of 65 events. The sensitivity of scintigraphy in prognosticating a major event or any event was, respectively, 55% and 58%, showing a negative predictive value of 90% and 83%, respectively. Diabetes mellitus, inconclusive stress electrocardiography, and a scintigraphic visualization of left ventricular enlargement were significant variables for the occurrence of a major event. On multivariate analysis, abnormal myocardial scintigraphy was a predictor of any event. CONCLUSION: Myocardial perfusion tomography with Technetium-99m may be used to identify high-risk patients after their first myocardial revascularization surgery.

  11. Myxoid Liposarcoma: Prognostic Factors and Metastatic Pattern in a Series of 148 Patients Treated at a Single Institution

    Directory of Open Access Journals (Sweden)

    Francesco Muratori

    2018-01-01

    Full Text Available Objectives. The authors reported a retrospective study on myxoid liposarcomas (MLs, evaluating factors that may influence overall survival (OS, local recurrence-free survival (LRFS, metastasis-free survival (MFS, and analyzing the metastatic pattern. Methods. 148 MLs were analyzed. The sites of metastases were investigated. Results. Margins (p = 0.002, grading (p = 0,0479, and metastasis (p < 0,0001 were significant risk factors affecting overall survival (OS. Type of presentation (p = 0.0243, grading (p = 0,0055, margin (p = 0.0001, and local recurrence (0.0437 were risk factors on metastasis-free survival (MFS. Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS and reported 55% extrapulmonary metastases and 45% pulmonary metastases. Conclusion. Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma.

  12. Circulating exosomal miR-27a and miR-130a act as novel diagnostic and prognostic biomarkers of colorectal cancer.

    Science.gov (United States)

    Wang, Shukui; Liu, Xiangxiang; Pan, Bei; Sun, Li; Chen, Xiaoxiang; Zeng, Kaixuan; Hu, Xiuxiu; Xu, Tao; Xu, Mu

    2018-05-08

    Colorectal cancer (CRC) is one of the most common cancers worldwide usually with poor prognosis due to the advanced stage when diagnosed. This study aimed to investigate whether specific circulating exosomal miRNAs could act as biomarkers for early diagnosis of CRC. A total of 369 peripheral blood samples were included in this study. In the discovery phase, circulating exosomal miR-27a and miR-130a were selected after synthetical analysis of two GEO datasets and TCGA database. The differential expression and diagnostic utility of miR-27a and miR-130a panel were validated using quantitative reverse-transcriptase PCR (qRT-PCR) and Receiver operating characteristic (ROC) curve analysis in subsequent training phase, validation phase and external validation phase. The prognosis of circulating exosomal miR-27a and miR-130a were investigated using the Kaplan-Meier method. The expression of exosomal miR-27a and miR-130a in plasma significantly increased in CRC. The area under ROC curves (AUCs) of miR-27a (miR-130a) were 0.773 (0.742) in the training phase, 0.82 (0.787) in the validation phase, and 0.746 (0.697) in the external validation phase. The combination of two miRNAs presented higher diagnostic utility for CRC (AUCs = 0.846, 0.898 and 0.801 for the training, validation, and external validation phases, respectively). CRC patients with high expression of circulating exosomal miR-27a or miR-130a underwent poorer prognosis. We identified a circulating exosomal miRNAs panel for the detection of CRC. The exosomal miR-27a and miR-130a panel in plasma may act as a non-invasive biomarker for early detection and predicting prognosis of CRC. Copyright ©2018, American Association for Cancer Research.

  13. Transcending the biomarker mindset: deciphering disease mechanisms at the single cell level.

    Science.gov (United States)

    Danna, Erika A; Nolan, Garry P

    2006-02-01

    The application of proteomics to disease research promises to enhance the understanding and treatment of many human maladies through the identification of molecular profiles associated with each disease. However, although much is made of the utility of molecular signatures as markers of disease state, insufficient emphasis is often placed on the simultaneous need for biological mechanism inquiry. Focused and detailed analyses of disease-associated signaling networks have the potential to be more mechanistically informative than large-scale proteomic profiling approaches, providing insight into the cellular processes involved in pathogenesis, disease progression and therapeutic resistance; while still providing diagnostic or clinical management direction. Phospho-specific flow cytometry provides a method for the analysis of pathological signaling networks, enabling the investigation of disease mechanisms at the single-cell level.

  14. Basal 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    International Nuclear Information System (INIS)

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel; Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano; Mar Munoz Sanchez, Maria del; Alvarez Cabellos, Ruth; Espinosa Aunion, Ruth

    2015-01-01

    To explore the relationship between basal 18 F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent 18 F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with 18 F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  15. Basal {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Garcia Vicente, Ana Maria; Soriano Castrejon, Angel [University General Hospital, Nuclear Medicine Department, Ciudad Real (Spain); Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano [University of Castilla-La Mancha, Department of Mathematics, Ciudad Real (Spain); Mar Munoz Sanchez, Maria del [Virgen de la Luz Hospital, Oncology Department, Cuenca (Spain); Alvarez Cabellos, Ruth [Virgen de la Salud Hospital, Oncology Department, Toledo (Spain); Espinosa Aunion, Ruth [La Mancha Centro Hospital, Oncology Department, Ciudad Real (Spain)

    2015-11-15

    To explore the relationship between basal {sup 18}F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent {sup 18}F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with {sup 18}F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

  16. Contemporary approach to neurologic prognostication of coma after cardiac arrest.

    Science.gov (United States)

    Ben-Hamouda, Nawfel; Taccone, Fabio S; Rossetti, Andrea O; Oddo, Mauro

    2014-11-01

    Coma after cardiac arrest (CA) is an important cause of admission to the ICU. Prognosis of post-CA coma has significantly improved over the past decade, particularly because of aggressive postresuscitation care and the use of therapeutic targeted temperature management (TTM). TTM and sedatives used to maintain controlled cooling might delay neurologic reflexes and reduce the accuracy of clinical examination. In the early ICU phase, patients' good recovery may often be indistinguishable (based on neurologic examination alone) from patients who eventually will have a poor prognosis. Prognostication of post-CA coma, therefore, has evolved toward a multimodal approach that combines neurologic examination with EEG and evoked potentials. Blood biomarkers (eg, neuron-specific enolase [NSE] and soluble 100-β protein) are useful complements for coma prognostication; however, results vary among commercial laboratory assays, and applying one single cutoff level (eg, > 33 μg/L for NSE) for poor prognostication is not recommended. Neuroimaging, mainly diffusion MRI, is emerging as a promising tool for prognostication, but its precise role needs further study before it can be widely used. This multimodal approach might reduce false-positive rates of poor prognosis, thereby providing optimal prognostication of comatose CA survivors. The aim of this review is to summarize studies and the principal tools presently available for outcome prediction and to describe a practical approach to the multimodal prognostication of coma after CA, with a particular focus on neuromonitoring tools. We also propose an algorithm for the optimal use of such multimodal tools during the early ICU phase of post-CA coma.

  17. The translational expression of ABCA2 and ABCA3 is a strong prognostic biomarker for multidrug resistance in pediatric acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Aberuyi N

    2017-07-01

    structures was revealed by protein tertiary structure prediction, whereas molecular docking analysis suggested similar binding of chemotherapy drugs and therefore a potentially similar role in determining the MDR.Conclusion: Our findings suggested, for the first time, that quantification of the protein level of ABCA2 and ABCA3 transporters had a prognostic impact on pediatric ALL MDR. Furthermore, the tertiary structure of ABCA2 was predicted for the first time, and docking analysis revealed a possible compensatory effect between ABCA2 and ABCA3 transporters, which may contribute to the efflux of cytotoxic drugs and, ultimately, to chemoresistance. Keywords: ABCA2 transporter, ABCA3 transporter, multidrug resistance, childhood acute lymphoblastic leukemia, molecular docking, tertiary structure

  18. Assessment of prognostic value of semiquantitative parameters on gated single photon emission computed tomography myocardial perfusion scintigraphy in a large middle eastern population

    International Nuclear Information System (INIS)

    Chavoshi, Maryam; Fard-Esfahani, Armaghan; Fallahi, Babak; Emami-Ardekani, Alireza; Beiki, Davood; Hassanzadeh-Rad, Arman; Eftekhari, Mohammad

    2005-01-01

    Coronary artery disease is the leading cause of mortality worldwide. The goal of this study is to determine the prognostic value of semiquantitative parameters of electrocardiogram-gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in a large Middle Eastern (Iranian) population. This study was a prospective study including all patients referred to our center for myocardial perfusion scan. The patients were followed annually up to 24 months and their survival information was collected. From 1148 patients, 473 (41.2%) men and 675 (58.8%) women, 40.6% had normal MPI, 13.3% near normal and 46.1% abnormal MPI. After follow-up of 929 patients, 97.4% of patients were alive, and 2.6% succumbed to cardiac deaths. Abnormal ejection fraction was related with cardiac events (P = 0.001), but neither transient ischemic dilation (TID) (P = 0.09) nor lung/heart ratio (P = 0.92) showed such relationship. Association between summed difference score (SDS) and soft cardiac events (P < 0.001) was significant. Summed motion score (SMS) and summed thickening score (STS) showed a significant relation with hard cardiac events, including myocardial infarction and cardiac death (P < 0.001 and P = 0.001, respectively). Totally, risk of all cardiac events was significantly higher in abnormal MPI group than normal group (P < 0.001, 0.02, and 0.025, respectively). No significant relationship was found between TID and total cardiac events (P = 0.478). Semiquantitative variables derived from gated SPECT MPI have independent prognostic value. Rate of total cardiac events is higher in patients with higher summed stress score and SDS. Total and hard cardiac events are higher in upper scores of functional parameters (SMS and STS). Total cardiac events are higher in patients with lower left ventricular ejection fraction

  19. Pitfalls in the analysis of volatile breath biomarkers: suggested solutions and SIFT-MS quantification of single metabolites

    Czech Academy of Sciences Publication Activity Database

    Smith, D.; Španěl, Patrik

    2015-01-01

    Roč. 9, č. 2 (2015), 022001 ISSN 1752-7155 Institutional support: RVO:61388955 Keywords : SIFT-MS * volatile biomarkers * quantifications Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 4.177, year: 2015

  20. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  1. Potential biomarkers for bipolar disorder: Where do we stand?

    Directory of Open Access Journals (Sweden)

    Rajesh Sagar

    2017-01-01

    Full Text Available Bipolar disorder (BD is a severe, recurrent mood disorder, associated with a significant morbidity and mortality, with high rates of suicides and medical comorbidities. There is a high risk of mood disorders among the first-degree relatives of patients with BD. In the current clinical practice, the diagnosis of BD is made by history taking, interview and behavioural observations, thereby lacking an objective, biological validation. This approach may result in underdiagnosis, misdiagnosis and eventually poorer outcomes. Due to the heterogeneity of BD, the possibility of developing a single, specific biomarker is still remote; however, there is a set of promising biomarkers which may serve as predictive, prognostic or treatment markers in the future. The review presents a critical appraisal and update on some of the most promising candidates for biomarkers, namely, neuroimaging markers, peripheral biomarkers and genetic markers, including a brief discussion on cognitive endophenotypes as indicative of genetic risk. The lessons learnt from other fields and specialties in medicine need to be applied to psychiatry to translate the knowledge from 'bench to bedside' by means of clinically useful biomarkers. Overall, the biomarkers may help in pushing the shift towards personalized medicine for psychiatric patients.

  2. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ranjit Chauhan

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

  3. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    International Nuclear Information System (INIS)

    Horton, Janet K.; Blitzblau, Rachel C.; Yoo, Sua; Geradts, Joseph; Chang, Zheng; Baker, Jay A.; Georgiade, Gregory S.; Chen, Wei; Siamakpour-Reihani, Sharareh; Wang, Chunhao; Broadwater, Gloria; Groth, Jeff; Palta, Manisha; Dewhirst, Mark; Barry, William T.; Duffy, Eileen A.

    2015-01-01

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  4. Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Horton, Janet K., E-mail: janet.horton@duke.edu [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Blitzblau, Rachel C.; Yoo, Sua [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Geradts, Joseph [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Chang, Zheng [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Baker, Jay A. [Department of Radiology, Duke University Medical Center, Durham, North Carolina (United States); Georgiade, Gregory S. [Department of Surgery, Duke University Medical Center, Durham, North Carolina (United States); Chen, Wei [Department of Bioinformatics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Siamakpour-Reihani, Sharareh; Wang, Chunhao [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Broadwater, Gloria [Department of Biostatistics: Duke Cancer Institute, Duke University Medical Center, Durham, North Carolina (United States); Groth, Jeff [Department of Pathology, Duke University Medical Center, Durham, North Carolina (United States); Palta, Manisha; Dewhirst, Mark [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); Barry, William T. [Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina (United States); Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Duffy, Eileen A. [Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina (United States); and others

    2015-07-15

    Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative, estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should

  5. Prognostic DNA Methylation Markers for Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Siri H. Strand

    2014-09-01

    Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

  6. Relationships between Endogenous Plasma Biomarkers of Constitutive Cytochrome P450 3A Activity and Single-Time-Point Oral Midazolam Microdose Phenotype in Healthy Subjects.

    Science.gov (United States)

    Woolsey, Sarah J; Beaton, Melanie D; Choi, Yun-Hee; Dresser, George K; Gryn, Steven E; Kim, Richard B; Tirona, Rommel G

    2016-04-01

    Due to high basal interindividual variation in cytochrome P450 3A (CYP3A) activity and susceptibility to drug interactions, there has been interest in the application of efficient probe drug phenotyping strategies, as well as endogenous biomarkers for assessment of in vivo CYP3A activity. The biomarkers 4β-hydroxycholesterol (4βHC) and 6β-hydroxycortisol (6βHCL) are sensitive to CYP3A induction and inhibition. However, their utility for the assessment of constitutive CYP3A activity remains uncertain. We investigated whether endogenous plasma biomarkers (4βHC and 6βHCL) are associated with basal CYP3A metabolic activity in healthy subjects assessed by a convenient single-time-point oral midazolam (MDZ) phenotyping strategy. Plasma 4βHC and 6βHCL metabolic ratios (MRs) were analysed in 51 healthy adult participants. CYP3A activity was determined after administration of an oral MDZ microdose (100 μg). Simple linear and multiple linear regression analyses were performed to assess relationships between MDZ oral clearance, biomarkers and subject covariates. Among study subjects, basal MDZ oral clearance, 4βHC and 6βHCL MRs ranged 6.5-, 10- and 13-fold, respectively. Participant age and alcohol consumption were negatively associated with MDZ oral clearance (p = 0.03 and p = 0.045, respectively), while weight and female sex were associated with lower plasma 4βHC MR (p = 0.0003 and p = 0.032, respectively). Neither 4βHC nor 6βHCL MRs were associated with MDZ oral clearance. Plasma 4βHC and 6βHCL MRs do not relate to MDZ single-time-point metabolic phenotype in the assessment of constitutive CYP3A activity among healthy individuals. © 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  7. Novel single-chain antibody GD3A10 defines a chondroitin sulfate biomarker for ovarian cancer

    NARCIS (Netherlands)

    Vallen, M.J.E.; Tilborg, A.G. van; Tesselaar, M.H.; Dam, G.B. ten; Bulten, J.; Kuppevelt, T.H. van; Massuger, L.F.A.G.

    2014-01-01

    AIMS: Ovarian cancer has the highest case-to-fatality-index of all gynecological cancers. In this study, tumor-related alterations in the extracellular matrix, especially regarding chondroitin sulfate glycosaminoglycans, are proposed as a novel biomarker in ovarian cancer. MATERIALS & METHODS: Phage

  8. A multi-institutional outcome and prognostic factor analysis of radiosurgery (RS) for resectable single brain metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Auchter, RM; Lamond, JP; Alexander, E; Buatti, JM; Chappell, RJ; Friedman, W; Kinsella, TJ; Levin, AB; Noyes, WR; Schultz, C; Loeffler, JS; Mehta, MP

    1995-07-01

    PURPOSE: Recent randomized trials comparing resection of single brain metastasis (BM) in selected patients (pts) followed by whole brain radiotherapy (WBRT) to WBRT alone demonstrated statistically significant survival advantage for surgery (Patchell, 1990 and Noordijk, 1994). This multi-institutional retrospective study was performed in similar pts who were treated with RS and WBRT to provide a baseline for comparison for a future randomized trial. MATERIALS AND METHODS: The RS databases of four institutions were reviewed to identify all pts who met the following criteria: single BM; age > 18; surgically resectable lesion; independently functional (KPS {>=} 70); non-radiosensitive histology (small cell, lymphoma, myeloma, germ cell excluded); no prior cranial surgery or WBRT. 122 of 533 pts with BM treated with RS met these criteria. Pts were categorized by: (a) status of the primary: 'absent' = complete resection, 26 pts; 'controlled' locally controlled with radiotherapy or chemotherapy, 70 pts; 'under treatment' = undergoing radiotherapy, 15 pts; 'active' = no definitive or successful treatment of the primary, 11 pts; (b) status of non-CNS metastasis: present=64 pts, absent=58 pts; (c) age: median=61, range 23-83; (d) KPS : KPS 70/80/90/100=20/26/44/32 pts; (e) histology: lung=58, melanoma=16, breast=13, renal=12,colon=9, other=10, unknown primary=4; (f) time from primary to BM: median=12 months, range=1-252 months; (g) gender: male=64, female=58; (h) tumor volume: median=2.68 cc, range=0.13-27.2 cc. RS was performed with a linear accelerator based technique (peripheral dose 10-27 Gy, median 17 Gy). WBRT was performed in all but 5 pts who refused it (range 25 - 40 Gy, median 37.5 Gy). RESULTS: The potential median follow-up for all pts is 123 weeks (wks). The overall local response rate is 59% (complete response = 25%, partial response = 34%). In field progression occurred in 17 patients (14%), with overall local control of 86%. Local control was highest for

  9. Biomarkers Prognostic for Elevated Intracranial Pressure

    Science.gov (United States)

    2016-03-01

    Orthopedic injury (n=20) iii) Exclusion of patients with polytrauma . It has been reported that serum ceruloplasmin (as well as copper) levels...inclusion of polytrauma patients in our results. We therefore identified the TBI patients with isolated head trauma, and compared the recorded...ceruloplasmin values between those with elevated ICP and those without. Figure 13 shows that when the patients with polytrauma were excluded from the

  10. Epigenetic prognostic biomarkers in colorectal cancer

    NARCIS (Netherlands)

    Benard, Anne

    2015-01-01

    Colorectal cancer is one of the most common diagnosed cancers worldwide, and is the second most important cause of cancer mortality in Europe. The current TNM staging system used at the time of diagnosis is insufficient, as patients with the same tumor stage show wide variations in survival and

  11. Comparison of 10 single and stepped methods to identify frail older persons in primary care: diagnostic and prognostic accuracy.

    Science.gov (United States)

    Sutorius, Fleur L; Hoogendijk, Emiel O; Prins, Bernard A H; van Hout, Hein P J

    2016-08-03

    Many instruments have been developed to identify frail older adults in primary care. A direct comparison of the accuracy and prevalence of identification methods is rare and most studies ignore the stepped selection typically employed in routine care practice. Also it is unclear whether the various methods select persons with different characteristics. We aimed to estimate the accuracy of 10 single and stepped methods to identify frailty in older adults and to predict adverse health outcomes. In addition, the methods were compared on their prevalence of the identified frail persons and on the characteristics of persons identified. The Groningen Frailty Indicator (GFI), the PRISMA-7, polypharmacy, the clinical judgment of the general practitioner (GP), the self-rated health of the older adult, the Edmonton Frail Scale (EFS), the Identification Seniors At Risk Primary Care (ISAR PC), the Frailty Index (FI), the InterRAI screener and gait speed were compared to three measures: two reference standards (the clinical judgment of a multidisciplinary expert panel and Fried's frailty criteria) and 6-years mortality or long term care admission. Data were used from the Dutch Identification of Frail Elderly Study, consisting of 102 people aged 65 and over from a primary care practice in Amsterdam. Frail older adults were oversampled. The accuracy of each instrument and several stepped strategies was estimated by calculating the area under the ROC-curve. Prevalence rates of frailty ranged from 14.8 to 52.9 %. The accuracy for recommended cut off values ranged from poor (AUC = 0.556 ISAR-PC) to good (AUC = 0.865 gait speed). PRISMA-7 performed best over two reference standards, GP predicted adversities best. Stepped strategies resulted in lower prevalence rates and accuracy. Persons selected by the different instruments varied greatly in age, IADL dependency, receiving homecare and mood. We found huge differences between methods to identify frail persons in prevalence

  12. Technical reproducibility of single-nucleotide and size-based DNA biomarker assessment using DNA extracted from formalin-fixed, paraffin-embedded tissues.

    Science.gov (United States)

    Zhang, Shenli; Tan, Iain B; Sapari, Nur S; Grabsch, Heike I; Okines, Alicia; Smyth, Elizabeth C; Aoyama, Toru; Hewitt, Lindsay C; Inam, Imran; Bottomley, Dan; Nankivell, Matthew; Stenning, Sally P; Cunningham, David; Wotherspoon, Andrew; Tsuburaya, Akira; Yoshikawa, Takaki; Soong, Richie; Tan, Patrick

    2015-05-01

    DNA extracted from formalin-fixed, paraffin-embedded (FFPE) tissues has been used in the past to analyze genetic polymorphisms. We evaluated the technical reproducibility of different types of assays for gene polymorphisms using DNA extracted from FFPE material. By using the MassARRAY iPLEX system, we investigated polymorphisms in DPYD (rs1801159 and rs3918290), UMPS (rs1801019), ERCC1 (rs11615), ERCC1 (rs3212986), and ERCC2 (rs13181) in 56 FFPE DNA samples. By using PCR, followed by size-based gel electrophoresis, we also examined TYMS 5' untranslated region 2R/3R repeats and GSTT1 deletions in 50 FFPE DNA samples and 34 DNAs extracted from fresh-frozen tissues and cell lines. Each polymorphism was analyzed by two independent runs. We found that iPLEX biomarker assays measuring single-nucleotide polymorphisms provided consistent concordant results. However, by using FFPE DNA, size-based PCR biomarkers (GSTT1 and TYMS 5' untranslated region) were discrepant in 32.7% (16/49, with exact 95% CI, 19.9%-47.5%; exact binomial confidence limit test) and 4.2% (2/48, with exact 95% CI, 0.5%-14.3%) of cases, respectively, whereas no discrepancies were observed using intact genomic DNA. Our findings suggest that DNA from FFPE material can be used to reliably test single-nucleotide polymorphisms. However, results based on size-based PCR biomarkers, and particularly GSTT1 deletions, using FFPE DNA need to be interpreted with caution. Independent repeated assays should be performed on all cases to assess potential discrepancies. Copyright © 2015 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  13. Meibomian gland dysfunction patients with novel Sjögren’s syndrome biomarkers benefit significantly from a single vectored thermal pulsation procedure: a retrospective analysis

    Directory of Open Access Journals (Sweden)

    Epitropoulos AT

    2017-04-01

    Full Text Available Alice T Epitropoulos,1,2 Krysta Goslin,2 Raman Bedi,3 Caroline A Blackie4 1Ophthalmic Surgeons and Consultants of Ohio, The Eye Center of Columbus, 2The Ohio State University Wexner Medical Center, Department of Ophthalmology, Columbus, OH, USA; 3Iris Advanced Eye Centre, Chandigarh, India; 4TearScience Inc., Morrisville, NC, USA Purpose: To measure the effects from a single vectored thermal pulsation treatment of the meibomian glands on dry eye signs and symptoms in patients who tested positively versus negatively for novel Sjögren’s syndrome (SS biomarkers. Methods: The retrospective study included the deidentified data of 102 eyes of 59 patients with dry eye and meibomian gland dysfunction (MGD, who were also tested for novel biomarkers for SS and underwent a single 12-minute LipiFlow thermal pulsation procedure. All patients were already being treated with individualized dry eye therapy but remained symptomatic. Meibomian gland secretion (MGS scores, Standard Patient Evaluation of Eye Dryness (SPEED questionnaire scores and tear breakup times (TBUTs before and 8 weeks after thermal pulsation treatment were analyzed. Results: Twenty-three patients tested positive for novel biomarkers of SS and 36 patients tested negative. At baseline, MGS, SPEED and TBUT of both SS-positive and SS-negative patients were equivalent. At 8 weeks’ post-treatment, mean MGS score, SPEED and TBUT were 13.0±7.8, 12.5±6.8 and 9.6±4.6, respectively, in SS-positive patients and 15.9±7.9, 10.0±6.3 and 8.3±4.6, respectively, in SS-negative patients (P<0.001. While the post-treatment MGS was significantly better in SS-negative patients than SS-positive (P=0.021, no significant difference between post-treatment SPEED and TBUT was observed between the two groups (P>0.05. Conclusion: LipiFlow treatment in MGD patients who were SS-positive for novel biomarkers of SS demonstrated improvement in signs and symptoms of dry eye. While improvement in MGS scores in SS

  14. Retinal single-layer analysis with optical coherence tomography shows inner retinal layer thinning in Huntington's disease as a potential biomarker.

    Science.gov (United States)

    Gulmez Sevim, Duygu; Unlu, Metin; Gultekin, Murat; Karaca, Cagatay

    2018-02-12

    There have been ongoing clinical trials of therapeutic agents in Huntington's disease (HD) which requires development of reliable biomarkers of disease progression. There have been studies in the literature with conflicting results on the involvement of retina in HD, and up to date there is not a study evaluating the single retinal layers in HD. We aimed to evaluate the specific retinal changes in HD and their usability as potential disease progression markers. This cross-sectional study used spectral-domain optical coherence tomography with automatic segmentation to measure peripapillary retinal nerve fiber layer (pRNFL) thickness and the thickness and volume of retinal layers in foveal scans of 15 patients with HD and 15 age- and sex-matched controls. Genetic testing results, disease duration, HD disease burden scores and Unified HD Rating Scales motor scores were acquired for the patients. Temporal pRNFL, macular RNFL (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer and outer plexiform layer thicknesses and IPL, retinal pigment epithelium and outer macular volume were found lower in HD compared to controls, while outer nuclear layer and outer retinal layer thickness were increased (p layer thicknesses, most significantly with mRNFL and GCL and disease progression markers. The outcomes of this study points out that retinal layers, most significantly mRNFL and GCL, are strongly correlated with the disease progression in HD and could serve as useful biomarkers for disease progression.

  15. Renal Cancer Biomarkers | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute's Laboratory of Proteomics and Analytical Technologies is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize diagnostic, therapeutic and prognostic cancer biomarkers from clinical specimens.

  16. Novel biomarkers for sepsis

    DEFF Research Database (Denmark)

    Larsen, Frederik Fruergaard; Petersen, J Asger

    2017-01-01

    BACKGROUND: Sepsis is a prevalent condition among hospitalized patients that carries a high risk of morbidity and mortality. Rapid recognition of sepsis as the cause of deterioration is desirable, so effective treatment can be initiated rapidly. Traditionally, diagnosis was based on presence of two...... or more positive SIRS criteria due to infection. However, recently published sepsis-3 criteria put more emphasis on organ dysfunction caused by infection in the definition of sepsis. Regardless of this, no gold standard for diagnosis exist, and clinicians still rely on a number of traditional and novel...... biomarkers to discriminate between patients with and without infection, as the cause of deterioration. METHOD: Narrative review of current literature. RESULTS: A number of the most promising biomarkers for diagnoses and prognostication of sepsis are presented. CONCLUSION: Procalcitonin, presepsin, CD64, su...

  17. Prognostic significance of classified extramural tumor deposits and extracapsular lymph node invasion in T3–4 colorectal cancer: a retrospective single-center study

    International Nuclear Information System (INIS)

    Yamano, Tomoki; Semba, Shuho; Noda, Masafumi; Yoshimura, Mie; Kobayashi, Masayoshi; Hamanaka, Michiko; Beppu, Naohito; Yano, Aya; Tsukamoto, Kiyoshi; Matsubara, Nagahide; Tomita, Naohiro

    2015-01-01

    Extramural tumor deposits (TDs) and extracapsular lymph node involvement (ECLNI) are considered to be poor prognostic factors in patients with T3–4, N0–2, M0 colorectal cancer (CRC). Although TDs are known to have multiple origins and pleomorphic features, the prognostic significances of the different type of TDs have not yet been established. We performed a retrospective review of 385 consecutive patients with T3–4, N0–2, M0 CRC who received curative resection at our institution between 2006 and 2012. We classified the TDs into two groups: invasive-type TD (iTD), which is characterized by the presence of lymphatic invasion, vascular invasion, perineural invasion, or undefined cancer cell clusters and nodular-type TD (nTD), which is characterized by a smooth or irregular-shaped tumor nodule other than an iTD. ECLNI was defined as invasion of cancer cells into capsular collagen tissues or adipose tissues beyond the capsular collagen. Multivariate analyses were used to assess the prognostic significance of iTD, ND, and ECLNI for relapse-free survival (RFS), disease-specific survival (DSS), and sites of recurrence. In patients without lymph node (LN) metastasis, the incidences of iTD and nTD were both in the range of 2–3 %. Conversely, in patients with LN metastasis, the incidences of iTD, nTD, and ECLNI were 31, 22, and 34 %, respectively. iTD, nTD, and ECLNI were all significant independent adverse factors for RFS in rectal cancer, and were all associated with pT, pN, and LN ratio. iTD was a significant independent adverse prognostic factor for DSS in rectal cancer, metastasis to the liver in colorectal cancer, and distant LN metastasis in colon cancer. ECLNI was a significant independent prognostic factor for RFS in colon cancer. Classifying TDs and assessing ECLNI may help establish significant prognostic factors for patients with T3–4, N0–2, M0 CRC

  18. Prognostic Factors in Patients with Primary Hemangiopericytomas of the Central Nervous System: A Series of 103 Cases at a Single Institution.

    Science.gov (United States)

    Zhu, Hongda; Duran, Daniel; Hua, Lingyang; Tang, Hailiang; Chen, Hong; Zhong, Ping; Zheng, Kang; Wang, Yongfei; Che, Xiaoming; Bao, Weimin; Wang, Yin; Xie, Qing; Gong, Ye

    2016-06-01

    Hemangiopericytoma (HPC) is a rare mesenchymal tumor that tends to affect the central nervous system and is associated with distant metastasis and a high recurrence rate. The purpose of this study was to analyze the prognostic factors in patients with primary HPC who received surgical treatment. This retrospective study reviewed all adult patients with primary HPC of the central nervous system treated from 2001 to 2009 at our institution. Clinical information, adjuvant radiation, and expression levels of Ki-67 and p53 were correlated with patient outcomes. The final analysis included 103 patients. The mean follow-up period was 75.9 months ± 36.5 (range, 1-165 months). There was a significant difference in progression-free survival (PFS) (P < 0.001) and overall survival (P = 0.014) between patients who underwent gross total resection versus subtotal resection. Expression of p53 was found in 48.5% of patients and showed utility as an independent unfavorable prognostic factor for PFS (P = 0.006). Multivariate analysis revealed that only extent of tumor resection (P = 0.004) and p53 expression (P = 0.024) were independent prognostic factors for PFS. Adjuvant radiation was found to extend PFS only in the p53-negative expression group (P = 0.044). Gross total resection significantly improves the outcome of patients with primary HPCs, whereas adjuvant radiation contributes significantly to PFS only in patients with negative p53 expression and in patients with incomplete resections. Extent of resection and p53 expression may serve as prognostic markers for the outcome of patients with primary HPC. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Multiple Sclerosis Cerebrospinal Fluid Biomarkers

    Directory of Open Access Journals (Sweden)

    Gavin Giovannoni

    2006-01-01

    Full Text Available Cerebrospinal fluid (CSF is the body fluid closest to the pathology of multiple sclerosis (MS. For many candidate biomarkers CSF is the only fluid that can be investigated. Several factors need to be standardized when sampling CSF for biomarker research: time/volume of CSF collection, sample processing/storage, and the temporal relationship of sampling to clinical or MRI markers of disease activity. Assays used for biomarker detection must be validated so as to optimize the power of the studies. A formal method for establishing whether or not a particular biomarker can be used as a surrogate end-point needs to be adopted. This process is similar to that used in clinical trials, where the reporting of studies has to be done in a standardized way with sufficient detail to permit a critical review of the study and to enable others to reproduce the study design. A commitment must be made to report negative studies so as to prevent publication bias. Pre-defined consensus criteria need to be developed for MS-related prognostic biomarkers. Currently no candidate biomarker is suitable as a surrogate end-point. Bulk biomarkers of the neurodegenerative process such as glial fibrillary acidic protein (GFAP and neurofilaments (NF have advantages over intermittent inflammatory markers.

  20. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Natalie Turner

    2014-03-01

    Full Text Available Circulating tumor cell (CTC count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  1. Single molecule upconversion-linked immunosorbent assay with extended dynamic range for the sensitive detection of diagnostic biomarkers

    Czech Academy of Sciences Publication Activity Database

    Farka, Z.; Matthias, J. M.; Hlaváček, Antonín; Skládal, P.; Gorris, H H.

    2017-01-01

    Roč. 89, NOV (2017), s. 11825-11830 ISSN 0003-2700 R&D Projects: GA ČR(CZ) GBP206/12/G014 Institutional support: RVO:68081715 Keywords : photon upconversion * immunoassay * single molecule detection Subject RIV: CB - Analytical Chemistry , Separation OBOR OECD: Analytical chemistry Impact factor: 6.320, year: 2016

  2. Single molecule upconversion-linked immunosorbent assay with extended dynamic range for the sensitive detection of diagnostic biomarkers

    Czech Academy of Sciences Publication Activity Database

    Farka, Z.; Matthias, J. M.; Hlaváček, Antonín; Skládal, P.; Gorris, H H.

    2017-01-01

    Roč. 89, NOV (2017), s. 11825-11830 ISSN 0003-2700 R&D Projects: GA ČR(CZ) GBP206/12/G014 Institutional support: RVO:68081715 Keywords : photon upconversion * immunoassay * single molecule detection Subject RIV: CB - Analytical Chemistry, Separation OBOR OECD: Analytical chemistry Impact factor: 6.320, year: 2016

  3. Biomarkers in Scleroderma: Progressing from Association to Clinical Utility.

    Science.gov (United States)

    Ligon, Colin; Hummers, Laura K

    2016-03-01

    Scleroderma is a heterogenous disease characterized by autoimmunity, a characteristic vasculopathy, and often widely varying extents of deep organ fibrosis. Recent advances in the understanding of scleroderma's evolution have improved the ability to identify subgroups of patients with similar prognosis in order to improve risk stratification, enrich clinical trials for patients likely to benefit from specific therapies, and identify promising therapeutic targets for intervention. High-throughput technologies have recently identified fibrotic and inflammatory effectors in scleroderma that exhibit strong prognostic ability and may be tied to disease evolution. Increasingly, the use of collections of assayed circulating proteins and patterns of gene expression in tissue has replaced single-marker investigations in understanding the evolution of scleroderma and in objectively characterizing disease extent. Lastly, identification of shared patterns of disease evolution has allowed classification of patients into latent disease subtypes, which may allow rapid clinical prognostication and targeted management in both clinical and research settings. The concept of biomarkers in scleroderma is expanding to include nontraditional measures of aggregate protein signatures and disease evolution. This review examines the recent advances in biomarkers with a focus on those approaches poised to guide prospective management or themselves serve as quantitative surrogate disease outcomes.

  4. Prognostic factors for medulloblastoma

    International Nuclear Information System (INIS)

    Jenkin, Derek; Al Shabanah, Mohamed; Al Shail, Essam; Gray, Alan; Hassounah, Maher; Khafaga, Yasser; Kofide, Amani; Mustafa, Mahmoud; Schultz, Henrik

    2000-01-01

    Purpose: To evaluate prognostic factors for medulloblastoma. Methods and Materials: One hundred and seventy-three consecutive patients with medulloblastoma, treated at King Faisal Specialist Hospital (KFSH) from 1988-1997, were reviewed. Eighty-four percent were children less than 15 years old. From 1988-1994, treatment was at the discretion of the investigator. From 1994-1998, patients entered a single-arm best practice protocol in which, in staged patients, the surgical intent was total resection, standard radiation treatment was defined, and adjuvant chemotherapy was given to a 'high-risk' subset. Results: For 150 patients who completed surgical and radiation treatment, the 5-year survival rate was 58%, compared with 0% for 16 patients who were unable to start or complete radiation treatment. For staged patients, the 5-year survival was M0 + M1, 78% and M2 + M3, 21% (p 14 years and gross cystic/necrotic features in the primary tumor. The size of the primary tumor, the degree of hydrocephalus at diagnosis, the presence of residual tumor in the post-operative CT/MRI, and the functional status of the patient prior to radiation treatment were not significant factors. Conclusions: Stage M0 + M1 was the most powerful favorable prognostic factor. In Saudi Arabia more patients present with advanced disseminated disease, 41% M2 + M3, than in the West, and this impacts adversely on overall survival. Total resection and standard radiation treatment were not sensitive prognostic factors in a treatment environment in which 78% of patients underwent at least 90% tumor resection and 60% received standard radiation treatment. In order to improve the proportion of patients able to complete radiation treatment, consideration should be given to limiting resection when the attainment of total resection is likely to be morbid, and to delaying rather than omitting radiation treatment in the patient severely compromised postoperatively

  5. Evaluation of human epidermal growth factor receptor 2 (HER2) single nucleotide polymorphisms (SNPs) in normal and breast tumor tissues and their link with breast cancer prognostic factors.

    Science.gov (United States)

    Furrer, Daniela; Lemieux, Julie; Côté, Marc-André; Provencher, Louise; Laflamme, Christian; Barabé, Frédéric; Jacob, Simon; Michaud, Annick; Diorio, Caroline

    2016-12-01

    Amplification of the human epidermal growth factor receptor 2 (HER2) gene is associated with worse prognosis and decreased overall survival in breast cancer patients. The HER2 gene contains several polymorphisms; two of the best-characterized HER2 polymorphisms are Ile655Val and Ala1170Pro. The aim of this study was to evaluate the association between these two HER2 polymorphisms in normal breast and breast cancer tissues and known breast cancer prognostic factors in a retrospective cohort study of 73 women with non-metastatic HER2-positive breast cancer. HER2 polymorphisms were assessed in breast cancer tissue and normal breast tissue using TaqMan assay. Ala1170Pro polymorphism in normal breast tissue was associated with age at diagnosis (p = 0.007), tumor size (p = 0.004) and lymphovascular invasion (p = 0.06). Similar significant associations in cancer tissues were observed. No association between the Ile655Val polymorphism and prognostic factors were observed. However, we found significant differences in the distribution of Ile655Val (p = 0.03) and Ala1170Pro (p = 0.01) genotypes between normal breast and breast tumor tissues. This study demonstrates that only the Ala1170Pro polymorphism is associated with prognostic factors in HER2-positive breast cancer patients. Moreover, our results suggest that both HER2 polymorphisms could play a significant role in carcinogenesis in non-metastatic HER2-positive breast cancer women. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Surface Prognostic Charts

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Surface Prognostic Charts are historical surface prognostic (forecast) charts created by the United States Weather Bureau. They include fronts, isobars, cloud, and...

  7. Phase II cancer clinical trials for biomarker-guided treatments.

    Science.gov (United States)

    Jung, Sin-Ho

    2018-01-01

    The design and analysis of cancer clinical trials with biomarker depend on various factors, such as the phase of trials, the type of biomarker, whether the used biomarker is validated or not, and the study objectives. In this article, we demonstrate the design and analysis of two Phase II cancer clinical trials, one with a predictive biomarker and the other with an imaging prognostic biomarker. Statistical testing methods and their sample size calculation methods are presented for each trial. We assume that the primary endpoint of these trials is a time to event variable, but this concept can be used for any type of endpoint.

  8. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon; Song, Ki Byung; Ramaiya, Nikhil H.; Tirumani, Sree Harsha; Hong, Seung-Mo

    2016-01-01

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  9. Prognostic value of CT findings to predict survival outcomes in patients with pancreatic neuroendocrine neoplasms: a single institutional study of 161 patients

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook; Kim, Hyoung Jung; Kim, Kyung Won; Byun, Jae Ho; Kim, So Yeon [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Seoul (Korea, Republic of); Song, Ki Byung [University of Ulsan College of Medicine, Department of Surgery, Asan Medical Center, Seoul (Korea, Republic of); Ramaiya, Nikhil H.; Tirumani, Sree Harsha [Harvard Medical School, Department of Imaging, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, MA (United States); Hong, Seung-Mo [University of Ulsan College of Medicine, Department of Pathology, Asan Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    To evaluate the prognostic value of CT to predict recurrence-free and overall survival in patients with pancreatic neuroendocrine neoplasms (PanNENs). Between January 2004 and December 2012, 161 consecutive patients who underwent preoperative triphasic CT and surgical resection with curative intent for PanNENs were identified. The tumour consistency, margin, presence of calcification, pancreatic duct dilatation, bile duct dilatation, vascular invasion, and hepatic metastases were evaluated. The tumour size, arterial enhancement ratio, and portal enhancement ratio were measured. The Cox proportional hazard model was used to determine the association between CT features and recurrence-free survival and overall survival. By multivariate analysis, tumour size (>3 cm) (hazard ratio, 3.314; p = 0.006), portal enhancement ratio (≤1.1) (hazard ratio, 2.718; p = 0.006), and hepatic metastases (hazard ratio, 4.374; p = 0.003) were independent significant variables for worse recurrence-free survival. Portal enhancement ratio (≤1.1) (hazard ratio, 5.951; p = 0.001) and hepatic metastases (hazard ratio, 4.122; p = 0.021) were independent significant variables for worse overall survival. Portal enhancement ratio (≤1.1) and hepatic metastases assessed on CT were common independent prognostic factors for worse recurrence-free survival and overall survival in patients with PanNENs. (orig.)

  10. Molecular Pathology: Predictive, Prognostic, and Diagnostic Markers in Uterine Tumors.

    Science.gov (United States)

    Ritterhouse, Lauren L; Howitt, Brooke E

    2016-09-01

    This article focuses on the diagnostic, prognostic, and predictive molecular biomarkers in uterine malignancies, in the context of morphologic diagnoses. The histologic classification of endometrial carcinomas is reviewed first, followed by the description and molecular classification of endometrial epithelial malignancies in the context of histologic classification. Taken together, the molecular and histologic classifications help clinicians to approach troublesome areas encountered in clinical practice and evaluate the utility of molecular alterations in the diagnosis and subclassification of endometrial carcinomas. Putative prognostic markers are reviewed. The use of molecular alterations and surrogate immunohistochemistry as prognostic and predictive markers is also discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Prognostic value of myocardial perfusion single-photon emission computed tomography for the prediction of future cardiac events in a Japanese population. A middle-term follow-up study

    International Nuclear Information System (INIS)

    Matsumoto, Naoya; Sato, Yuichi; Suzuki, Yasuyuki

    2007-01-01

    The prognostic value of rest 201 Tl/stress 99m Tc-tetrofosmin myocardial perfusion single-photon emission computed tomography (SPECT) for the prediction of future hard cardiac events, including acute myocardial infarction (AMI), unstable angina (UAP) and cardiac death, and the implications for risk stratification has not yet been defined in a Japanese population. The 1,988 patients who underwent rest 201 Tl/stress 99m Tc-tetrofosmin SPECT were identified and followed up for the occurrence of AMI, UAP and cardiac death. The mean follow-up interval was 26.9±15.8 months. The 142 patients were revascularized within 60 days after SPECT and they were censored from the prognostic analysis. Summed stress score (SSS), summed rest score and summed difference score (SDS) were calculated using a 5-point scoring (Normal: 0, No uptake: 4) and a 20-segment model; 22 cases of myocardial infarction, 31 of UAP and 22 cardiac deaths occurred (1.2%, 1.7% and 1.2%, respectively). Multivariate Cox regression analysis showed that hypertension (Wald 6.37, p<0.05) and SDS (Wald 8.77, p<0.01) were independent predictors of AMI and UAP. Advanced age (Wald 16.0, p<0.001), SSS (Wald 10.9, p<0.01) and SDS (Wald 4.58, p<0.05) were independent predictors of cardiac death. Myocardial perfusion SPECT yields prognostic information toward the identification of acute coronary syndrome and cardiac death. (author)

  12. Single-Nucleotide Variations in Cardiac Arrhythmias: Prospects for Genomics and Proteomics Based Biomarker Discovery and Diagnostics

    Directory of Open Access Journals (Sweden)

    Ayman Abunimer

    2014-03-01

    Full Text Available Cardiovascular diseases are a large contributor to causes of early death in developed countries. Some of these conditions, such as sudden cardiac death and atrial fibrillation, stem from arrhythmias—a spectrum of conditions with abnormal electrical activity in the heart. Genome-wide association studies can identify single nucleotide variations (SNVs that may predispose individuals to developing acquired forms of arrhythmias. Through manual curation of published genome-wide association studies, we have collected a comprehensive list of 75 SNVs associated with cardiac arrhythmias. Ten of the SNVs result in amino acid changes and can be used in proteomic-based detection methods. In an effort to identify additional non-synonymous mutations that affect the proteome, we analyzed the post-translational modification S-nitrosylation, which is known to affect cardiac arrhythmias. We identified loss of seven known S-nitrosylation sites due to non-synonymous single nucleotide variations (nsSNVs. For predicted nitrosylation sites we found 1429 proteins where the sites are modified due to nsSNV. Analysis of the predicted S-nitrosylation dataset for over- or under-representation (compared to the complete human proteome of pathways and functional elements shows significant statistical over-representation of the blood coagulation pathway. Gene Ontology (GO analysis displays statistically over-represented terms related to muscle contraction, receptor activity, motor activity, cystoskeleton components, and microtubule activity. Through the genomic and proteomic context of SNVs and S-nitrosylation sites presented in this study, researchers can look for variation that can predispose individuals to cardiac arrhythmias. Such attempts to elucidate mechanisms of arrhythmia thereby add yet another useful parameter in predicting susceptibility for cardiac diseases.

  13. LABORATORY BIOMARKERS FOR ANKYLOSING SPONDYLITIS

    Directory of Open Access Journals (Sweden)

    E. N. Aleksandrova

    2017-01-01

    Full Text Available Ankylosing spondylitis (AS is a chronic inflammatory disease from a group of spondyloarthritis (SpA, which is characterized by lesions of the sacroiliac joints and spine with the common involvement of entheses and peripheral joints in the pathological process. Advances in modern laboratory medicine have contributed to a substantial expansion of the range of pathogenetic, diagnostic, and prognostic biomarkers of AS. As of now, there are key pathogenetic biomarkers of AS (therapeutic targets, which include tumor necrosis factor-α (TNF-α, interleukin 17 (IL-17, and IL-23. Among the laboratory diagnostic and prognostic biomarkers, HLA-B27 and C-reactive protein are of the greatest value in clinical practice; the former for the early diagnosis of the disease and the latter for the assessment of disease activity, the risk of radiographic progression and the efficiency of therapy. Anti-CD74 antibodies are a new biomarker that has high sensitivity and specificity values in diagnosing axial SpA at an early stage. A number of laboratory biomarkers, including calprotectin, matrix metalloproteinase-3 (MMP-3, vascular endothelial growth factor, Dickkopf-1 (Dkk-1, and C-terminal telopeptide of type II collagen (CTX II do not well reflect disease activity, but may predict progressive structural changes in the spine and sacroiliac joints in AS. Blood calprotectin level monitoring allows the effective prediction of a response to therapy with TNF inhibitors and anti-IL-17А monoclonal antibodies. The prospects for the laboratory diagnosis of AS are associated with the clinical validation of candidate biomarkers during large-scale prospective cohort studies and with a search for new proteomic, transcriptomic and genomic markers, by using innovative molecular and cellular technologies.

  14. Prognostic factors in adult soft tissue sarcoma treated with surgery combined with radiotherapy: a retrospective single-center study on 164 patients

    Directory of Open Access Journals (Sweden)

    Ling Cai

    2013-10-01

    Full Text Available The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT, with or without chemotherapy (CXT, for soft-tissue sarcoma (STS in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%, or without (52% CXT, 15% preoperative RT with (5%, or without (10% CXT, surgery alone (7%, or RT alone (2% with or without CXT. The median follow-up was 60 months (range 6-292. Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS, disease-free survival (DFS, local control (LC and distant metastases-free survival (DMFS were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS. This study confirms that in a multidisciplinary setting, STS have a fairly good prognosis. A number of prognostic and predictive factors, including the role of surgery combined with RT, were identified. Regarding RT, a dose of

  15. Prognostic Factors in Adult Soft Tissue Sarcoma Treated with Surgery Combined with Radiotherapy: A Retrospective Single-Center Study on 164 Patients

    Science.gov (United States)

    Cai, Ling; Mirimanoff, René-Olivier; Mouhsine, Elyazid; Guillou, Louis; Leyvraz, Pierre-Francois; Leyvraz, Serge; Gay, Beatrice; Matzinger, Oscar; Ozsahin, Mahmut; Zouhair, Abderrahim

    2013-01-01

    The aim of the present study is to assess the disease profile, outcome and prognostic factors in patients treated with surgery combined with radiotherapy (RT), with or without chemotherapy (CXT), for soft-tissue sarcoma (STS) in a multidisciplinary setting. One hundred and sixty-four patients with STS treated between 1980 and 2010 at the Centre Hospitalier Universitaire Vaudois were enrolled in this retrospective study. Seventy-six percent of patients underwent postoperative RT with (24%), or without (52%) CXT, 15% preoperative RT with (5%), or without (10%) CXT, surgery alone (7%), or RT alone (2%) with or without CXT. The median follow-up was 60 months (range 6-292). Local failure was observed in 18%, and distant failure in 21% of the patients. Overall survival (OS), diseasefree survival (DFS), local control (LC) and distant metastases-free survival (DMFS) were 88%, 68%, 83%, and 79% at 5 years, and 80%, 56%, 76%, and 69% at 10 years, respectively. In univariate analyses, favorable prognostic factors for OS, DFS, and DMFS were tumor size 6 cm or less, World Health Organization (WHO)/Zubrod score 0, and stage 2 or less. Age and superficial tumors were favorable only for OS and DMFS respectively. STS involving the extremities had a better outcome regarding DFS and LC. Histological grade 2 or less was favorable for DFS, DMFS, and LC. Radical surgery was associated with better LC and DMFS. RT dose more than 60 Gy was favorable for OS, DFS, and LC. In multivariate analyses, independent factors were age for OS; tumor size for OS, DFS and DMFS; WHO/Zubrod score for OS, DFS and LC; hemoglobin level for DFS; site for DFS and LC; tumor depth for DMFS; histological grade for DFS and LC; surgical procedure for LC and DMFS; and RT dose for OS. This study confirms that in a multidisciplinary setting, STS have a fairly good prognosis. A number of prognostic and predictive factors, including the role of surgery combined with RT, were identified. Regarding RT, a dose of more than

  16. A biomarker model of sublethal genotoxicity (DNA single-strand breaks and adducts) using the sentinel organism Aporrectodea longa in spiked soil

    International Nuclear Information System (INIS)

    Martin, Francis L.; Piearce, Trevor G.; Hewer, Alan; Phillips, David H.; Semple, Kirk T.

    2005-01-01

    There is a need to develop risk biomarkers during the remediation of contaminated land. We employed the earthworm, Aporrectodea longa (Ude), to determine whether genotoxicity measures could be applied to this organism's intestinal tissues. Earthworms were added, for 24 h or 7 days, to soil samples spiked with benzo[a]pyrene (B[a]P) and/or lindane. After exposure, intestinal tissues (crop/gizzard or intestine) were removed prior to the measurement in disaggregated cells of DNA single-strand breaks (SSBs) by the alkaline comet assay. Damage was quantified by comet tail length (CTL, μm). B[a]P 24-h exposure induced dose-related increases (P 32 P-postlabelling, showed a two-adduct-spot pattern. This preliminary investigation suggests that earthworm tissues may be incorporated into genotoxicity assays to facilitate hazard identification within terrestrial ecosystems. - Sublethal genotoxicity in the sentinel organism A. longa can be used to monitor the effects of contaminants in soil

  17. Estimating central tendency from a single spot measure: A closed-form solution for lognormally distributed biomarker data for risk assessment at the individual level.

    Science.gov (United States)

    Pleil, Joachim D; Sobus, Jon R

    2016-01-01

    Exposure-based risk assessment employs large cross-sectional data sets of environmental and biomarker measurements to predict population statistics for adverse health outcomes. The underlying assumption is that long-term (many years) latency health problems including cancer, autoimmune and cardiovascular disease, diabetes, and asthma are triggered by lifetime exposures to environmental stressors that interact with the genome. The aim of this study was to develop a specific predictive method that provides the statistical parameters for chronic exposure at the individual level based upon a single spot measurement and knowledge of global summary statistics as derived from large data sets. This is a profound shift in exposure and health statistics in that it begins to answer the question "How large is my personal risk?" rather than just providing an overall population-based estimate. This approach also holds value for interpreting exposure-based risks for small groups of individuals within a community in comparison to random individuals from the general population.

  18. Non-metastatic Ewing's sarcoma family of tumors of bone in adolescents and adults: prognostic factors and clinical outcome-single institution results.

    Science.gov (United States)

    Oksüz, Didem Colpan; Tural, Deniz; Dincbas, Fazilet Öner; Dervisoglu, Sergülen; Turna, Hande; Hiz, Murat; Kantarci, Fatih; Ceylaner, Beyhan; Koca, Sedat; Mandel, Nil Molinas

    2014-01-01

    There is limited data regarding outcomes of Ewing's sarcoma family of tumors in adolescents and adults compared with the same tumors in childhood. The aim of the study was to analyze prognostic factors and treatment results in a cohort of adolescents and adults with non-metastatic skeletal Ewing's sarcoma family of tumors. From 1992-2008, 90 adolescents and adults with Ewing's sarcoma family of tumors of the bone were referred to our institution. Sixty-five (72%) non-metastatic patients with analyzable data and treated in our institution were retrospectively evaluated. All patients were treated with alternated chemotherapy regimens administered every 3 weeks. The local treatment modality was selected according to tumor and patient characteristics. The median age was 21 years (range, 13-50). Most patients (74%) were >17 years of age. Forty-six percent of the tumors were located in the extremities. Local therapy was surgery in 45 patients and radiotherapy alone in 19 patients. Twenty-one patients received preoperative and 13 patients postoperative radiotherapy. Median follow-up was 43 months (range, 7-167). The 5-year event-free and overall survival rates for all patients were 44% and 49%, respectively. On univariate survival analysis, event-free and overall survival were worse for patients >17 years of age, tumor size >8 cm in diameter, an axial location, positive surgical margins, and poor histopathological response (<90% necrosis). Age, tumor site and tumor size on event-free and overall survival remained significant on multivariate analysis. We identified age, tumor size, and tumor site as independent prognostic factors, in accord with the Western literature. These patients require novel treatment modalities.

  19. [Cellular microparticles, potential useful biomarkers in the identification of cerebrovascular accidents].

    Science.gov (United States)

    Anglés-Cano, Eduardo; Vivien, Denis

    2009-10-01

    The clinical utility of biomarkers depends on their ability to identify high-risk individuals in order to establish preventive, diagnostic or therapeutic measures. Currently, no practical, rapid and sensitive test is available for the diagnosis of acute ischemic stroke. A number of soluble molecules have been identified that are merely associated to these cerebrovascular accidents. Despite this association not a single molecule has the characteristics of a true biomarker directly involved in the pathophysiology of ischemic stroke-none of them is organ-specific and may therefore be elevated in the context of medical comorbidities. When explored as a combination of biomarkers, e.g. matrix metalloproteinase 9, brain natriuretic protein, D-dimer, protein S100B, the question still remains whether serial biomarker analysis provides additional prognostic information. Even S100B, a glial activation protein, has a low specificity for acute ischemic stroke because it may originate from extracranial sources. Current knowledge from the field of cell-derived microparticles suggests that these membrane fragments may represent reliable biomarkers as they are cell-specific and are released early in the pathophysiological cascade of a disease. These microparticles can be found not only in the cerebrospinal fluid but also in tears and circulating blood in case of blood-brain barrier dysfunction. They represent a new challenge in stroke diagnosis and management.

  20. Fluid biomarkers in multiple system atrophy

    DEFF Research Database (Denmark)

    Laurens, Brice; Constantinescu, Radu; Freeman, Roy

    2015-01-01

    Despite growing research efforts, no reliable biomarker currently exists for the diagnosis and prognosis of multiple system atrophy (MSA). Such biomarkers are urgently needed to improve diagnostic accuracy, prognostic guidance and also to serve as efficacy measures or surrogates of target...... engagement for future clinical trials. We here review candidate fluid biomarkers for MSA and provide considerations for further developments and harmonization of standard operating procedures. A PubMed search was performed until April 24, 2015 to review the literature with regard to candidate blood...... and cerebrospinal fluid (CSF) biomarkers for MSA. Abstracts of 1760 studies were retrieved and screened for eligibility. The final list included 60 studies assessing fluid biomarkers in patients with MSA. Most studies have focused on alpha-synuclein, markers of axonal degeneration or catecholamines. Their results...

  1. RECENT ADVANCES IN BIOMARKERS IN SEVERE BURNS.

    Science.gov (United States)

    Ruiz-Castilla, Mireia; Roca, Oriol; Masclans, Joan R; Barret, Joan P

    2016-02-01

    The pathophysiology of burn injuries is tremendously complex. A thorough understanding is essential for correct treatment of the burned area and also to limit the appearance of organ dysfunction, which, in fact, is a key determinant of morbidity and mortality. In this context, research into biomarkers may play a major role. Biomarkers have traditionally been considered an important area of medical research: the measurement of certain biomarkers has led to a better understanding of pathophysiology, while others have been used either to assess the effectiveness of specific treatments or for prognostic purposes. Research into biomarkers may help to improve the prognosis of patients with severe burn injury. The aim of the present clinical review is to discuss new evidence of the value of biomarkers in this setting.

  2. The Indian Consensus Document on cardiac biomarker

    Directory of Open Access Journals (Sweden)

    I. Satyamurthy

    2014-01-01

    Full Text Available Despite recent advances, the diagnosis and management of heart failure evades the clinicians. The etiology of congestive heart failure (CHF in the Indian scenario comprises of coronary artery disease, diabetes mellitus and hypertension. With better insights into the pathophysiology of CHF, biomarkers have evolved rapidly and received diagnostic and prognostic value. In CHF biomarkers prove as measures of the extent of pathophysiological derangement; examples include biomarkers of myocyte necrosis, myocardial remodeling, neurohormonal activation, etc. In CHF biomarkers act as indicators for the presence, degree of severity and prognosis of the disease, they may be employed in combination with the present conventional clinical assessments. These make the biomarkers feasible options against the present expensive measurements and may provide clinical benefits.

  3. Charophyte electrogenesis as a biomarker for assessing the risk from low-dose ionizing radiation to a single plant cell

    International Nuclear Information System (INIS)

    Sevriukova, Olga; Kanapeckaite, Auste; Lapeikaite, Indre; Kisnieriene, Vilma; Ladygiene, Rima; Sakalauskas, Vidmantas

    2014-01-01

    The impact of low-dose ionizing radiation on the electrical signalling pattern and membrane properties of the characea Nitellopsis obtusa was examined using conventional glass-microelectrode and voltage-clamp techniques. The giant cell was exposed to a ubiquitous radionuclide of high biological importance – tritium – for low-dose irradiation. Tritium was applied as tritiated water with an activity concentration of 15 kBq L −1 (an external dose rate that is approximately 0.05 μGy h −1 above the background radiation level); experiments indicated that this was the lowest effective concentration. Investigating the dynamics of electrical excitation of the plasma membrane (action potential) showed that exposing Characeae to tritium for half an hour prolonged the repolarization phase of the action potential by approximately 35%: the repolarization rate decreased from 39.2 ± 3.1 mV s −1 to 25.5 ± 1,8 mV s −1 due to tritium. Voltage-clamp measurements showed that the tritium exposure decreased the Cl – efflux and Ca 2+ influx involved in generating an action potential by approximately 27% (Δ = 12.4 ± 1.1 μA cm −2 ) and 64% (Δ = −5.3 ± 0.4 μA cm −2 ), respectively. The measured alterations in the action potential dynamics and in the chloride and calcium ion transport due to the exogenous low-dose tritium exposure provide the basis for predicting possible further impairments of plasma membrane regulatory functions, which subsequently disturb essential physiological processes of the plant cell. - Highlights: • We show some cellular details of the impact of low-dose ionizing radiation on biota. • Giant green algae cells provides a useful tool for studying HTO toxicity to a single plant cell. • Rapid real-time electrophysiological methods allowed to determine low dose tritium effect on transmembrane ion fluxes. • Pattern of charophyte cell membrane electrical excitation encodes tritium-caused alteration in cell homeostasis

  4. Pharmacogenomic Biomarkers

    Directory of Open Access Journals (Sweden)

    Sandra C. Kirkwood

    2002-01-01

    Full Text Available Pharmacogenomic biomarkers hold great promise for the future of medicine and have been touted as a means to personalize prescriptions. Genetic biomarkers for disease susceptibility including both Mendelian and complex disease promise to result in improved understanding of the pathophysiology of disease, identification of new potential therapeutic targets, and improved molecular classification of disease. However essential to fulfilling the promise of individualized therapeutic intervention is the identification of drug activity biomarkers that stratify individuals based on likely response to a particular therapeutic, both positive response, efficacy, and negative response, development of side effect or toxicity. Prior to the widespread clinical application of a genetic biomarker multiple scientific studies must be completed to identify the genetic variants and delineate their functional significance in the pathophysiology of a carefully defined phenotype. The applicability of the genetic biomarker in the human population must then be verified through both retrospective studies utilizing stored or clinical trial samples, and through clinical trials prospectively stratifying patients based on the biomarker. The risk conferred by the polymorphism and the applicability in the general population must be clearly understood. Thus, the development and widespread application of a pharmacogenomic biomarker is an involved process and for most disease states we are just at the beginning of the journey towards individualized therapy and improved clinical outcome.

  5. miR-345 in metastatic colorectal cancer: a non-invasive biomarker for clinical outcome in non-KRAS mutant patients treated with 3rd line cetuximab and irinotecan

    DEFF Research Database (Denmark)

    Schou, Jakob V; Rossi, Simona; Jensen, Benny V

    2014-01-01

    for overall survival (OS) in patients with metastatic colorectal cancer (mCRC) treated with cetuximab and irinotecan. METHODS: From 138 patients with mCRC in 3rd line therapy with cetuximab and irinotecan in a prospective phase II study, 738 pretreatment miRNAs were isolated and profiled from whole blood...... to treatment with cetuximab and irinotecan. CONCLUSION: We identified miR-345 in whole blood as a potential biomarker for clinical outcome. MiR-345 was a single prognostic biomarker for both OS and PFS in all patients and also in the non-KRAS mutant population....

  6. Prognostic significance of MCM2, Ki-67 and gelsolin in non-small cell lung cancer

    International Nuclear Information System (INIS)

    Yang, Jun; Tan, Dongfeng; Ramnath, Nithya; Moysich, Kirsten B; Asch, Harold L; Swede, Helen; Alrawi, Sadir J; Huberman, Joel; Geradts, Joseph; Brooks, John SJ

    2006-01-01

    Uncontrolled proliferation and increased motility are hallmarks of neoplastic cells, therefore markers of proliferation and motility may be valuable in assessing tumor progression and prognosis. MCM2 is a member of the minichromosome maintenance (MCM) protein family. It plays critical roles in the initiation of DNA replication and in replication fork movement, and is intimately related to cell proliferation. Ki-67 is a proliferation antigen that is expressed during all but G 0 phases of the cell cycle. Gelsolin is an actin-binding protein that regulates the integrity of the actin cytoskeletal structure and facilitates cell motility. In this study, we assessed the prognostic significance of MCM2 and Ki-67, two markers of proliferation, and gelsolin, a marker of motility, in non-small cell lung cancer (NSCLC). 128 patients with pathologically confirmed, resectable NSCLC (stage I-IIIA) were included. Immunohistochemistry was utilized to measure the expressions of these markers in formalin-fixed, paraffin-embedded tumor tissues. Staining and scoring of MCM2, Ki-67 and gelsolin was independently performed. Analyses were performed to evaluate the prognostic significance of single expression of each marker, as well as the prognostic significance of composite expressions of MCM2 and gelsolin. Cox regression and Kaplan-Meier survival analysis were used for statistical analysis. Of the three markers, higher levels of gelsolin were significantly associated with an increased risk of death (adjusted RR = 1.89, 95% CI = 1.17–3.05, p = 0.01), and higher levels of MCM2 were associated with a non-significant increased risk of death (adjusted RR = 1.36, 95% CI = 0.84–2.20, p = 0.22). Combined, adjusted analyses revealed a significantly poor prognostic effect for higher expression of MCM2 and gelsolin compared to low expression of both biomarkers (RR = 2.32, 95% CI = 1.21–4.45, p = 0.01). Ki-67 did not display apparent prognostic effect in this study sample. The results suggest

  7. Clinical Correlates and Prognostic Value of Plasma Galectin-3 Levels in Degenerative Aortic Stenosis: A Single-Center Prospective Study of Patients Referred for Invasive Treatment

    Directory of Open Access Journals (Sweden)

    Beata Bobrowska

    2017-04-01

    Full Text Available Galectin-3 (Gal-3, a β-galactoside-binding lectin, has been implicated in myocardial fibrosis, development of left ventricular (LV dysfunction and transition from compensated LV hypertrophy to overt heart failure (HF, being a novel prognostic marker in HF. Risk stratification is crucial for the choice of the optimal therapy in degenerative aortic stenosis (AS, affecting elderly subjects with coexistent diseases. Our aim was to assess correlates and prognostic value of circulating Gal-3 in real-world patients with degenerative AS referred for invasive treatment. Gal-3 levels were measured at admission in 80 consecutive patients with symptomatic degenerative AS (mean age: 79 ± 8 years; aortic valve area (AVA index: 0.4 ± 0.1 cm2/m2. The therapeutic strategy was chosen following a dedicated multidisciplinary team-oriented approach, including surgical valve replacement (n = 11, transcatheter valve implantation (n = 19, balloon aortic valvuloplasty (BAV (n = 25 and optimal medical therapy (n = 25. Besides routine echocardiographic indices, valvulo-arterial impedance (Zva, an index of global LV afterload, was computed. There were 22 deaths over a median follow-up of 523 days. Baseline Gal-3 correlated negatively with estimated glomerular filtration rate (eGFR (r = −0.61, p < 0.001 and was unrelated to age, symptomatic status, AVA index, LV ejection fraction, LV mass index or Zva. For the study group as a whole, Gal-3 tended to predict mortality (Gal-3 >17.8 vs. Gal-3 <17.8 ng/mL; hazard ratio (HR: 2.03 (95% confidence interval, 0.88–4.69, p = 0.09, which was abolished upon adjustment for eGFR (HR: 1.70 (0.61–4.73, p = 0.3. However, in post-BAV patients multivariate-adjusted pre-procedural Gal-3 was associated with worse survival (HR: 7.41 (1.52–36.1, p = 0.01 regardless of eGFR. In conclusion, the inverse eGFR–Gal-3 relationship underlies a weak association between Gal-3 and adverse outcome in patients with degenerative AS referred for

  8. Early prognostication markers in cardiac arrest patients treated with hypothermia.

    Science.gov (United States)

    Karapetkova, M; Koenig, M A; Jia, X

    2016-03-01

    Established prognostication markers, such as clinical findings, electroencephalography (EEG) and biochemical markers, used by clinicians to predict neurological outcome after cardiac arrest (CA) are altered under therapeutic hypothermia (TH) conditions and their validity remains uncertain. MEDLINE and Embase were searched for evidence on the current standards for neurological outcome prediction for out-of-hospital CA patients treated with TH and the validity of a wide range of prognostication markers. Relevant studies that suggested one or several established biomarkers and multimodal approaches for prognostication are included and reviewed. Whilst the prognostic accuracy of various tests after TH has been questioned, pupillary light reflexes and somatosensory evoked potentials are still strongly associated with negative outcome for early prognostication. Increasingly, EEG background activity has also been identified as a valid predictor for outcome after 72 h after CA and a preferred prognostic method in clinical settings. Neuroimaging techniques, such as magnetic resonance imaging and computed tomography, can identify functional and structural brain injury but are not readily available at the patient's bedside because of limited availability and high costs. A multimodal algorithm composed of neurological examination, EEG-based quantitative testing and somatosensory evoked potentials, in conjunction with newer magnetic resonance imaging sequences, if available, holds promise for accurate prognostication in CA patients treated with TH. In order to avoid premature withdrawal of care, prognostication should be performed more than 72 h after CA. © 2015 EAN.

  9. The Role of Large-Format Histopathology in Assessing Subgross Morphological Prognostic Parameters: A Single Institution Report of 1000 Consecutive Breast Cancer Cases

    Directory of Open Access Journals (Sweden)

    Tibor Tot

    2012-01-01

    Full Text Available Breast cancer subgross morphological parameters (disease extent, lesion distribution, and tumor size provide significant prognostic information and guide therapeutic decisions. Modern multimodality radiological imaging can determine these parameters with increasing accuracy in most patients. Large-format histopathology preserves the spatial relationship of the tumor components and their relationship to the resection margins and has clear advantages over traditional routine pathology techniques. We report a series of 1000 consecutive breast cancer cases worked up with large-format histology with detailed radiological-pathological correlation. We confirmed that breast carcinomas often exhibit complex subgross morphology in both early and advanced stages. Half of the cases were extensive tumors and occupied a tissue space ≥40 mm in its largest dimension. Because both in situ and invasive tumor components may exhibit unifocal, multifocal, and diffuse lesion distribution, 17 different breast cancer growth patterns can be observed. Combining in situ and invasive tumor components, most cases fall into three aggregate growth patterns: unifocal (36%, multifocal (35%, and diffuse (28%. Large-format histology categories of tumor size and disease extent were concordant with radiological measurements in approximately 80% of the cases. Noncalcified, low-grade in situ foci, and invasive tumor foci <5 mm were the most frequent causes of discrepant findings.

  10. Myocardial technetium-99m sestamibi single-photon emission tomography as a prognostic tool in coronary artery disease: multivariate analysis in a long-term prospective study

    International Nuclear Information System (INIS)

    Zanco, P.; Zampiero, A.; Favero, A.; Borsato, N.; Chierichetti, F.; Rubello, D.; Saitta, B.; Ferlin, G.

    1995-01-01

    A prospective study was started in 1988 and at present 176 consecutive, and thus unselected, patients have been enrolled. All of them have been submitted to stress-rest MIBI SPET for the diagnosis or evaluation of CAD; 147 patients (121 males and 26 females, aged 53±9 years) have completed a surveillance period of at least 36 months following the scintigraphic study (range 36-60 months, mean 43). Sixty-one patients had a documented previous myocardial infarction. The mean pre-test likelihood of CAD was 44% in the patients without prior infarction. The main anamnestic, clinical, EKG and scintigraphic findings were evaluated and statistically correlated with the incidence of ensuing cardiac events using both univariate (chi-square test) and multivariate analysis (logistic regression model). Twenty-nine patients suffered from a cardiac event during the follow-up period (i.e. three cardiac deaths, six myocardial infarctions and 20 cases of unstable angina). Statistical multivariate analysis identified MIBI scan as the only highly significant and independent prognostic predictor. In detail, the most important scintigraphic parameters were the presence of a reversible defect and the extension of the stress perfusion defect. The presence of typical angina proved to be a slightly significant predictor, while no other examined parameter showed a significant correlation with a bad prognosis. In conclusion, MIBI SPET can be considered a useful tool in the risk stratification of CAD patients. (orig.). With 3 tabs

  11. Work ability as prognostic risk marker of disability pension : Single-item work ability score versus multi-item work ability index

    NARCIS (Netherlands)

    Roelen, C.A.M.; Rhenen, van W.; Groothoff, J.W.; Klink, van der J.J.L.; Twisk, W.R.; Heymans, M.W.

    2014-01-01

    Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP.

  12. Work ability as prognostic risk marker of disability pension: single-item work ability score versus multi-item work ability index

    NARCIS (Netherlands)

    Roelen, C.A.M.; van Rhenen, W.; Groothoff, J.W.; van der Klink, J.J.L.; Twisk, J.W.R.; Heymans, M.W.

    2014-01-01

    Objectives Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP. Methods This

  13. Work ability as prognostic risk marker of disability pension : single-item work ability score versus multi-item work ability index

    NARCIS (Netherlands)

    Roelen, Corne A. M.; van Rhenen, Willem; Groothoff, Johan W.; van der Klink, Jac J. L.; Twisk, Jos W. R.; Heymans, Martijn W.

    Objectives Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP. Methods This

  14. Prognostic and predictive factors in colorectal cancer.

    Science.gov (United States)

    Bolocan, A; Ion, D; Ciocan, D N; Paduraru, D N

    2012-01-01

    Colorectal cancer (CRC) is an important public health problem; it is a leading cause of cancer mortality in the industrialized world, second to lung cancer: each year there are nearly one million new cases of CRC diagnosed worldwide and half a million deaths (1). This review aims to summarise the most important currently available markers for CRC that provide prognostic or predictive information. Amongst others, it covers serum markers such as CEA and CA19-9, markers expressed by tumour tissues, such as thymidylate synthase, and also the expression/loss of expression of certain oncogenes and tumour suppressor genes such as K-ras and p53. The prognostic value of genomic instability, angiogenesis and proliferative indices, such as the apoptotic index, are discussed. The advent of new therapies created the pathway for a personalized approach of the patient. This will take into consideration the complex genetic mechanisms involved in tumorigenesis, besides the classical clinical and pathological stagings. The growing number of therapeutic agents and known molecular targets in oncology lead to a compulsory study of the clinical use of biomarkers with role in improving response and survival, as well as in reducing toxicity and establishing economic stability. The potential predictive and prognostic biomarkers which have arisen from the study of the genetic basis of colorectal cancer and their therapeutical significance are discussed. RevistaChirurgia.

  15. Prognostic Performance Metrics

    Data.gov (United States)

    National Aeronautics and Space Administration — This chapter presents several performance metrics for offline evaluation of prognostics algorithms. A brief overview of different methods employed for performance...

  16. Prognostics for Microgrid Components

    Science.gov (United States)

    Saxena, Abhinav

    2012-01-01

    Prognostics is the science of predicting future performance and potential failures based on targeted condition monitoring. Moving away from the traditional reliability centric view, prognostics aims at detecting and quantifying the time to impending failures. This advance warning provides the opportunity to take actions that can preserve uptime, reduce cost of damage, or extend the life of the component. The talk will focus on the concepts and basics of prognostics from the viewpoint of condition-based systems health management. Differences with other techniques used in systems health management and philosophies of prognostics used in other domains will be shown. Examples relevant to micro grid systems and subsystems will be used to illustrate various types of prediction scenarios and the resources it take to set up a desired prognostic system. Specifically, the implementation results for power storage and power semiconductor components will demonstrate specific solution approaches of prognostics. The role of constituent elements of prognostics, such as model, prediction algorithms, failure threshold, run-to-failure data, requirements and specifications, and post-prognostic reasoning will be explained. A discussion on performance evaluation and performance metrics will conclude the technical discussion followed by general comments on open research problems and challenges in prognostics.

  17. A gene expression signature of retinoblastoma loss-of-function is a predictive biomarker of resistance to palbociclib in breast cancer cell lines and is prognostic in patients with ER positive early breast cancer.

    Science.gov (United States)

    Malorni, Luca; Piazza, Silvano; Ciani, Yari; Guarducci, Cristina; Bonechi, Martina; Biagioni, Chiara; Hart, Christopher D; Verardo, Roberto; Di Leo, Angelo; Migliaccio, Ilenia

    2016-09-13

    Palbociclib is a CDK4/6 inhibitor that received FDA approval for treatment of hormone receptor positive (HR+) HER2 negative (HER2neg) advanced breast cancer. To better personalize patients treatment it is critical to identify subgroups that would mostly benefit from it. We hypothesize that complex alterations of the Retinoblastoma (Rb) pathway might be implicated in resistance to CDK4/6 inhibitors and aim to investigate whether signatures of Rb loss-of-function would identify breast cancer cell lines resistant to palbociclib. We established a gene expression signature of Rb loss-of-function (RBsig) by identifying genes correlated with E2F1 and E2F2 expression in breast cancers within The Cancer Genome Atlas. We assessed the RBsig prognostic role in the METABRIC and in a comprehensive breast cancer meta-dataset. Finally, we analyzed whether RBsig would discriminate palbociclib-sensitive and -resistant breast cancer cells in a large RNA sequencing-based dataset. The RBsig was associated with RB1 genetic status in all tumors (p <7e-32) and in luminal or basal subtypes (p < 7e-11 and p < 0.002, respectively). The RBsig was prognostic in the METABRIC dataset (discovery: HR = 1.93 [1.5-2.4] p = 1.4e-08; validation: HR = 2.01 [1.6-2.5] p = 1.3e-09). Untreated and endocrine treated patients with estrogen receptor positive breast cancer expressing high RBsig had significantly worse recurrence free survival compared to those with low RBsig (HR = 2.37 [1.8 - 3.2] p = 1.87e-08 and HR = 2.62 [1.9- 3.5] p = 8.6e-11, respectively). The RBsig was able to identify palbociclib resistant and sensitive breast cancer cells (ROC AUC = 0,7778). Signatures of RB loss might be helpful in personalizing treatment of patients with HR+/HER2neg breast cancer. Further validation in patients receiving palbociclib is warranted.

  18. Prognostic value of myocardial perfusion single photon emission computed tomography for major adverse cardiac cerebrovascular and renal events in patients with chronic kidney disease: results from first year of follow-up of the Gunma-CKD SPECT multicenter study

    Energy Technology Data Exchange (ETDEWEB)

    Kasama, Shu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Cardiovascular Hospital of Central Japan (Kitakanto Cardiovascular Hospital), Department of Cardiovascular Medicine, Gunma (Japan); Toyama, Takuji [Department of Cardiovascular Medicine, Gunma Prefectural Cardiovascular Center, Maebashi (Japan); Sato, Makito [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Tatebayashi Kosei Hospital, Department of Internal Medicine, Gunma (Japan); Sano, Hirokazu [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Isesaki Municipal Hospital, Department of Cardiovascular Medicine, Isesaki (Japan); Ueda, Tetsuya [Fujioka General Hospital, Division of Cardiology, Fujioka (Japan); Sasaki, Toyoshi [Takasaki General Medical Center, Division of Cardiology, Takasaki (Japan); Nakahara, Takehiro; Kurabayashi, Masahiko [Gunma University Graduate School of Medicine, Department of Medicine and Biological Science (Cardiovascular Medicine), Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi (Japan)

    2016-02-15

    Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. We examined whether stress myocardial perfusion single photon emission computed tomography (SPECT) provides reliable prognostic markers for these patients. In this multicenter, prospective cohort trial from the Gunma-CKD SPECT study protocol, patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml per 1.73 m{sup 2}] undergoing stress {sup 99m}Tc-tetrofosmin SPECT for suspected or possible ischemic heart disease were initially followed for 1 year, with the following study endpoints: primary, the occurrence of cardiac deaths (CDs), and secondary, major adverse cardiac, cerebrovascular, and renal events (MACCREs). The summed stress score (SSS), summed rest score, and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Left ventricular end-diastolic volume, end-systolic volume (ESV), and ejection fraction were measured using electrocardiogram-gated SPECT. During the first year of follow-up, 69 of 299 patients experienced MACCREs (CD, n = 7; non-fatal myocardial infarction, n = 3; hospitalization for heart failure, n = 13; cerebrovascular accident, n = 1; need for revascularization, n = 38; and renal failure, i.e., hemodialysis initiation, n = 7). ESV and SSS were associated with CDs (p < 0.05), and eGFR and SDS were associated with MACCREs (p < 0.05), in multivariate logistic analysis. Patients with high ESV and high SSS had a significantly higher CD rate during the first year than the other CKD patient subgroups (p < 0.05). Patients with low eGFR and high SDS had a significantly higher MACCRE rate than the other subgroups (p < 0.05). Myocardial perfusion SPECT can provide reliable prognostic markers for patients with CKD. (orig.)

  19. Prognostic value of myocardial perfusion single photon emission computed tomography for major adverse cardiac cerebrovascular and renal events in patients with chronic kidney disease: results from first year of follow-up of the Gunma-CKD SPECT multicenter study

    International Nuclear Information System (INIS)

    Kasama, Shu; Toyama, Takuji; Sato, Makito; Sano, Hirokazu; Ueda, Tetsuya; Sasaki, Toyoshi; Nakahara, Takehiro; Kurabayashi, Masahiko; Higuchi, Tetsuya; Tsushima, Yoshito

    2016-01-01

    Patients with chronic kidney disease (CKD) have an increased risk of adverse cardio-cerebrovascular events. We examined whether stress myocardial perfusion single photon emission computed tomography (SPECT) provides reliable prognostic markers for these patients. In this multicenter, prospective cohort trial from the Gunma-CKD SPECT study protocol, patients with CKD [estimated glomerular filtration rate (eGFR) < 60 min/ml per 1.73 m 2 ] undergoing stress 99m Tc-tetrofosmin SPECT for suspected or possible ischemic heart disease were initially followed for 1 year, with the following study endpoints: primary, the occurrence of cardiac deaths (CDs), and secondary, major adverse cardiac, cerebrovascular, and renal events (MACCREs). The summed stress score (SSS), summed rest score, and summed difference score (SDS) were estimated with the standard 17-segment, 5-point scoring model. Left ventricular end-diastolic volume, end-systolic volume (ESV), and ejection fraction were measured using electrocardiogram-gated SPECT. During the first year of follow-up, 69 of 299 patients experienced MACCREs (CD, n = 7; non-fatal myocardial infarction, n = 3; hospitalization for heart failure, n = 13; cerebrovascular accident, n = 1; need for revascularization, n = 38; and renal failure, i.e., hemodialysis initiation, n = 7). ESV and SSS were associated with CDs (p < 0.05), and eGFR and SDS were associated with MACCREs (p < 0.05), in multivariate logistic analysis. Patients with high ESV and high SSS had a significantly higher CD rate during the first year than the other CKD patient subgroups (p < 0.05). Patients with low eGFR and high SDS had a significantly higher MACCRE rate than the other subgroups (p < 0.05). Myocardial perfusion SPECT can provide reliable prognostic markers for patients with CKD. (orig.)

  20. Rivaroxaban for Preventing Atherothrombotic Events in People with Acute Coronary Syndrome and Elevated Cardiac Biomarkers: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

    Science.gov (United States)

    Pandor, Abdullah; Pollard, Daniel; Chico, Tim; Henderson, Robert; Stevenson, Matt

    2016-05-01

    As part of its Single Technology Appraisal process, the National Institute for Health and Care Excellence (NICE) invited the company that manufactures rivaroxaban (Xarelto, Bayer) to submit evidence of the clinical and cost effectiveness of rivaroxaban for the prevention of adverse outcomes in patients after the acute management of acute coronary syndrome (ACS). The School of Health and Related Research Technology Appraisal Group at the University of Sheffield was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a critical review of the evidence for the clinical and cost effectiveness of the technology, based upon the company's submission to NICE. The evidence was derived mainly from a randomised, double-blind, phase III, placebo-controlled trial of rivaroxaban (either 2.5 or 5 mg twice daily) in patients with recent ACS [unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI)]. In addition, all patients received antiplatelet therapy [aspirin alone or aspirin and a thienopyridine either as clopidogrel (approximately 99 %) or ticlopidine (approximately 1 %) according to national or local guidelines]. The higher dose of rivaroxaban (5 mg twice daily) did not form part of the marketing authorisation. A post hoc subgroup analysis of the licensed patients who had ACS with elevated cardiac biomarkers (that is, patients with STEMI and NSTEMI) without prior stroke or transient ischaemic stroke showed that compared with standard care, the addition of rivaroxaban (2.5 mg twice daily) to existing antiplatelet therapy reduced the composite endpoint of cardiovascular mortality, myocardial infarction or stroke, but increased the risk of major bleeding and intracranial haemorrhage. However, there were a number of limitations in the evidence base that warrant caution in its interpretation. In particular, the evidence may be confounded because of the post hoc subgroup

  1. DNA Methylation Biomarkers: Cancer and Beyond

    Directory of Open Access Journals (Sweden)

    Thomas Mikeska

    2014-09-01

    Full Text Available Biomarkers are naturally-occurring characteristics by which a particular pathological process or disease can be identified or monitored. They can reflect past environmental exposures, predict disease onset or course, or determine a patient’s response to therapy. Epigenetic changes are such characteristics, with most epigenetic biomarkers discovered to date based on the epigenetic mark of DNA methylation. Many tissue types are suitable for the discovery of DNA methylation biomarkers including cell-based samples such as blood and tumor material and cell-free DNA samples such as plasma. DNA methylation biomarkers with diagnostic, prognostic and predictive power are already in clinical trials or in a clinical setting for cancer. Outside cancer, strong evidence that complex disease originates in early life is opening up exciting new avenues for the detection of DNA methylation biomarkers for adverse early life environment and for estimation of future disease risk. However, there are a number of limitations to overcome before such biomarkers reach the clinic. Nevertheless, DNA methylation biomarkers have great potential to contribute to personalized medicine throughout life. We review the current state of play for DNA methylation biomarkers, discuss the barriers that must be crossed on the way to implementation in a clinical setting, and predict their future use for human disease.

  2. Prognostic methods in medicine

    NARCIS (Netherlands)

    Lucas, P. J.; Abu-Hanna, A.

    1999-01-01

    Prognosis--the prediction of the course and outcome of disease processes--plays an important role in patient management tasks like diagnosis and treatment planning. As a result, prognostic models form an integral part of a number of systems supporting these tasks. Furthermore, prognostic models

  3. Aircraft Anomaly Prognostics, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Ridgetop Group will leverage its proven Electromechanical Actuator (EMA) prognostics methodology to develop an advanced model-based actuator prognostic reasoner...

  4. Prognostic Gene Expression Profiles in Breast Cancer

    DEFF Research Database (Denmark)

    Sørensen, Kristina Pilekær

    Each year approximately 4,800 Danish women are diagnosed with breast cancer. Several clinical and pathological factors are used as prognostic and predictive markers to categorize the patients into groups of high or low risk. Around 90% of all patients are allocated to the high risk group...... clinical courses, and they may be useful as novel prognostic biomarkers in breast cancer. The aim of the present project was to predict the development of metastasis in lymph node negative breast cancer patients by RNA profiling. We collected and analyzed 82 primary breast tumors from patients who...... and the time of event. Previous findings have shown that high expression of the lncRNA HOTAIR is correlated with poor survival in breast cancer. We validated this finding by demonstrating that high HOTAIR expression in our primary tumors was significantly associated with worse prognosis independent...

  5. Development of a blood-based molecular biomarker test for identification of schizophrenia before disease onset

    NARCIS (Netherlands)

    M.K. Chan (Man K.); M.-O. Krebs (M-O); D. Cox; P.C. Guest (Paul); R.H. Yolken; H. Rahmoune (Hassan); M. Rothermundt (Matthias); J. Steiner (Johann); F.M. Leweke (Marcus); N.J.M. van Beveren (Nico); D. Niebuhr (David); N. Weber (Natalya); D. Cowan (David); P. Suarez-Pinilla; B. Crespo-Facorro (Benedicto); C. Mam-Lam-Fook; J. Bourgin; R.J. Wenstrup (Richard); R.R. Kaldate; J.D. Cooper (Jason); S. Bahn (Sabine)

    2015-01-01

    markdownabstractRecent research efforts have progressively shifted towards preventative psychiatry and prognostic identification of individuals before disease onset. We describe the development of a serum biomarker test for the identification of individuals at risk of developing schizophrenia based

  6. Candidate immune biomarkers for radioimmunotherapy.

    Science.gov (United States)

    Levy, Antonin; Nigro, Giulia; Sansonetti, Philippe J; Deutsch, Eric

    2017-08-01

    Newly available immune checkpoint blockers (ICBs), capable to revert tumor immune tolerance, are revolutionizing the anticancer armamentarium. Recent evidence also established that ionizing radiation (IR) could produce antitumor immune responses, and may as well synergize with ICBs. Multiple radioimmunotherapy combinations are thenceforth currently assessed in early clinical trials. Past examples have highlighted the need for treatment personalization, and there is an unmet need to decipher immunological biomarkers that could allow selecting patients who could benefit from these promising but expensive associations. Recent studies have identified potential predictive and prognostic immune assays at the cellular (tumor microenvironment composition), genomic (mutational/neoantigen load), and peripheral blood levels. Within this review, we collected the available evidence regarding potential personalized immune biomarker-directed radiation therapy strategies that might be used for patient selection in the era of radioimmunotherapy. Copyright © 2017. Published by Elsevier B.V.

  7. Bioinformatics and biomarker discovery "Omic" data analysis for personalized medicine

    CERN Document Server

    Azuaje, Francisco

    2010-01-01

    This book is designed to introduce biologists, clinicians and computational researchers to fundamental data analysis principles, techniques and tools for supporting the discovery of biomarkers and the implementation of diagnostic/prognostic systems. The focus of the book is on how fundamental statistical and data mining approaches can support biomarker discovery and evaluation, emphasising applications based on different types of "omic" data. The book also discusses design factors, requirements and techniques for disease screening, diagnostic and prognostic applications. Readers are provided w

  8. Work ability as prognostic risk marker of disability pension: single-item work ability score versus multi-item work ability index.

    Science.gov (United States)

    Roelen, Corné A M; van Rhenen, Willem; Groothoff, Johan W; van der Klink, Jac J L; Twisk, Jos W R; Heymans, Martijn W

    2014-07-01

    Work ability predicts future disability pension (DP). A single-item work ability score (WAS) is emerging as a measure for work ability. This study compared single-item WAS with the multi-item work ability index (WAI) in its ability to identify workers at risk of DP. This prospective cohort study comprised 11 537 male construction workers, who completed the WAI at baseline and reported DP after a mean 2.3 years of follow-up. WAS and WAI were calibrated for DP risk predictions with the Hosmer-Lemeshow (H-L) test and their ability to discriminate between high- and low-risk construction workers was investigated with the area under the receiver operating characteristic curve (AUC). At follow-up, 336 (3%) construction workers reported DP. Both WAS [odds ratio (OR) 0.72, 95% confidence interval (95% CI) 0.66-0.78] and WAI (OR 0.57, 95% CI 0.52-0.63) scores were associated with DP at follow-up. The WAS showed miscalibration (H-L model χ (�)=10.60; df=3; P=0.01) and poorly discriminated between high- and low-risk construction workers (AUC 0.67, 95% CI 0.64-0.70). In contrast, calibration (H-L model χ �=8.20; df=8; P=0.41) and discrimination (AUC 0.78, 95% CI 0.75-0.80) were both adequate for the WAI. Although associated with the risk of future DP, the single-item WAS poorly identified male construction workers at risk of DP. We recommend using the multi-item WAI to screen for risk of DP in occupational health practice.

  9. Network-based identification of biomarkers coexpressed with multiple pathways.

    Science.gov (United States)

    Guo, Nancy Lan; Wan, Ying-Wooi

    2014-01-01

    Unraveling complex molecular interactions and networks and incorporating clinical information in modeling will present a paradigm shift in molecular medicine. Embedding biological relevance via modeling molecular networks and pathways has become increasingly important for biomarker identification in cancer susceptibility and metastasis studies. Here, we give a comprehensive overview of computational methods used for biomarker identification, and provide a performance comparison of several network models used in studies of cancer susceptibility, disease progression, and prognostication. Specifically, we evaluated implication networks, Boolean networks, Bayesian networks, and Pearson's correlation networks in constructing gene coexpression networks for identifying lung cancer diagnostic and prognostic biomarkers. The results show that implication networks, implemented in Genet package, identified sets of biomarkers that generated an accurate prediction of lung cancer risk and metastases; meanwhile, implication networks revealed more biologically relevant molecular interactions than Boolean networks, Bayesian networks, and Pearson's correlation networks when evaluated with MSigDB database.

  10. Molecular alterations and biomarkers in colorectal cancer

    Science.gov (United States)

    Grady, William M.; Pritchard, Colin C.

    2013-01-01

    The promise of precision medicine is now a clinical reality. Advances in our understanding of the molecular genetics of colorectal cancer genetics is leading to the development of a variety of biomarkers that are being used as early detection markers, prognostic markers, and markers for predicting treatment responses. This is no more evident than in the recent advances in testing colorectal cancers for specific molecular alterations in order to guide treatment with the monoclonal antibody therapies cetuximab and panitumumab, which target the epidermal growth factor receptor (EGFR). In this review, we update a prior review published in 2010 and describe our current understanding of the molecular pathogenesis of colorectal cancer and how these alterations relate to emerging biomarkers for early detection and risk stratification (diagnostic markers), prognosis (prognostic markers), and the prediction of treatment responses (predictive markers). PMID:24178577

  11. Prognostics of Power MOSFET

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and...

  12. Plasma YKL-40: a potential new cancer biomarker?

    DEFF Research Database (Denmark)

    Johansen, Julia S; Schultz, Nicolai A; Jensen, Benny V

    2009-01-01

    tissue remodeling. Plasma levels of YKL-40 are elevated in a subgroup of patients with primary or advanced cancer compared with age-matched healthy subjects, but also in patients with many different diseases characterized by inflammation. Elevated plasma YKL-40 levels are an independent prognostic...... by inflammation. Large prospective, longitudinal clinical cancer studies are needed to determine if plasma YKL-40 is a new cancer biomarker, or is mainly a biomarker of inflammation....

  13. Impact of body weight, low energy diet and gastric bypass on drug bioavailability, cardiovascular risk factors and metabolic biomarkers: protocol for an open, non-randomised, three-armed single centre study (COCKTAIL).

    Science.gov (United States)

    Hjelmesæth, Jøran; Åsberg, Anders; Andersson, Shalini; Sandbu, Rune; Robertsen, Ida; Johnson, Line Kristin; Angeles, Philip Carlo; Hertel, Jens Kristoffer; Skovlund, Eva; Heijer, Maria; Ek, Anna-Lena; Krogstad, Veronica; Karlsen, Tor-Ivar; Christensen, Hege; Andersson, Tommy B; Karlsson, Cecilia

    2018-05-29

    Roux-en-Y gastric bypass (GBP) is associated with changes in cardiometabolic risk factors and bioavailability of drugs, but whether these changes are induced by calorie restriction, the weight loss or surgery per se, remains uncertain. The COCKTAIL study was designed to disentangle the short-term (6 weeks) metabolic and pharmacokinetic effects of GBP and a very low energy diet (VLED) by inducing a similar weight loss in the two groups. This open, non-randomised, three-armed, single-centre study is performed at a tertiary care centre in Norway. It aims to compare the short-term (6 weeks) and long-term (2 years) effects of GBP and VLED on, first, bioavailability and pharmacokinetics (24 hours) of probe drugs and biomarkers and, second, their effects on metabolism, cardiometabolic risk factors and biomarkers. The primary outcomes will be measured as changes in: (1) all six probe drugs by absolute bioavailability area under the curve (AUC oral /AUC iv ) of midazolam (CYP3A4 probe), systemic exposure (AUC oral ) of digoxin and rosuvastatin and drug:metabolite ratios for omeprazole, losartan and caffeine, levels of endogenous CYP3A biomarkers and genotypic variation, changes in the expression and activity data of the drug-metabolising, drug transport and drug regulatory proteins in biopsies from various organs and (2) body composition, cardiometabolic risk factors and metabolic biomarkers. The COCKTAIL protocol was reviewed and approved by the Regional Committee for Medical and Health Research Ethics (Ref: 2013/2379/REK sørøst A). The results will be disseminated to academic and health professional audiences and the public via presentations at conferences, publications in peer-reviewed journals and press releases and provided to all participants. NCT02386917. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Prognostic Factors for Tumor Recurrence after a 12-Year, Single-Center Experience of Liver Transplantations in Patients with Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Matteo Cescon

    2010-01-01

    Full Text Available Background. Factors affecting outcomes after orthotopic liver transplantation (OLT for hepatocellular carcinoma (HCC have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12% patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio=2.88; 95% C.I.=1.43–5.80; =.003, preoperative tumor treatments (Odds Ratio=4.84; 95% C.I.=1.42–16.42; =.01, and microvascular invasion (Odds Ratio=4.82; 95% C.I.=1.87–12.41; =.001 were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.

  15. Biomarkers of PTSD: military applications and considerations

    OpenAIRE

    Amy Lehrner; Rachel Yehuda

    2014-01-01

    Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk fo...

  16. Biomarkers of PTSD: military applications and considerations

    Directory of Open Access Journals (Sweden)

    Amy Lehrner

    2014-08-01

    Full Text Available Background: Although there are no established biomarkers for posttraumatic stress disorder (PTSD as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. Objective: This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Method: Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Results: Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Conclusions: Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  17. Biomarkers of PTSD: military applications and considerations.

    Science.gov (United States)

    Lehrner, Amy; Yehuda, Rachel

    2014-01-01

    Although there are no established biomarkers for posttraumatic stress disorder (PTSD) as yet, biological investigations of PTSD have made progress identifying the pathophysiology of PTSD. Given the biological and clinical complexity of PTSD, it is increasingly unlikely that a single biomarker of disease will be identified. Rather, investigations will more likely identify different biomarkers that indicate the presence of clinically significant PTSD symptoms, associate with risk for PTSD following trauma exposure, and predict or identify recovery. While there has been much interest in PTSD biomarkers, there has been less discussion of their potential clinical applications, and of the social, legal, and ethical implications of such biomarkers. This article will discuss possible applications of PTSD biomarkers, including the social, legal, and ethical implications of such biomarkers, with an emphasis on military applications. Literature on applications of PTSD biomarkers and on potential ethical and legal implications will be reviewed. Biologically informed research findings hold promise for prevention, assessment, treatment planning, and the development of prophylactic and treatment interventions. As with any biological indicator of disorder, there are potentially positive and negative clinical, social, legal, and ethical consequences of using such biomarkers. Potential clinical applications of PTSD biomarkers hold promise for clinicians, patients, and employers. The search for biomarkers of PTSD should occur in tandem with an interdisciplinary discussion regarding the potential implications of applying biological findings in clinical and employment settings.

  18. Localized primary gastrointestinal diffuse large B cell lymphoma received a surgical approach: an analysis of prognostic factors and comparison of staging systems in 101 patients from a single institution.

    Science.gov (United States)

    Zhang, Shengting; Wang, Li; Yu, Dong; Shen, Yang; Cheng, Shu; Zhang, Li; Qian, Ying; Shen, Zhixiang; Li, Qinyu; Zhao, Weili

    2015-08-15

    Diffuse large B cell lymphoma (DLBCL) represents the most common histological subtype of primary gastrointestinal lymphoma and is a heterogeneous group of disease. Prognostic characterization of individual patients is an essential prerequisite for a proper risk-based therapeutic choice. Clinical and pathological prognostic factors were identified, and predictive value of four previously described prognostic systems were assessed in 101 primary gastrointestinal DLBCL (PG-DLBCL) patients with localized disease, including Ann Arbor staging with Musshoff modification, International Prognostic Index (IPI), Lugano classification, and Paris staging system. Univariate factors correlated with inferior survival time were clinical parameters [age>60 years old, multiple extranodal/gastrointestinal involvement, elevated serum lactate dehydrogenase and β2-microglobulin, and decreased serum albumin], as well as pathological parameters (invasion depth beyond serosa, involvement of regional lymph node or adjacent tissue, Ki-67 index, and Bcl-2 expression). Major independent variables of adverse outcome indicated by multivariate analysis were multiple gastrointestinal involvement. In patients unfit for Rituximab but received surgery, radical surgery significantly prolonged the survival time, comparing with alleviative surgery. Addition of Rituximab could overcome the negative prognostic effect of alleviative surgery. Among the four prognostic systems, IPI and Lugano classification clearly separated patients into different risk groups. IPI was able to further stratify the early-stage patients of Lugano classification into groups with distinct prognosis. Radical surgery might be proposed for the patients unfit for Rituximab treatment, and a combination of clinical and pathological staging systems was more helpful to predict the disease outcome of PG-DLBCL patients.

  19. The morphological growth patterns of colorectal liver metastases are prognostic for overall survival

    DEFF Research Database (Denmark)

    Nielsen, Kåre; Rolff, Hans C; Eefsen, Rikke L

    2014-01-01

    Colorectal metastases in the liver grow according to three histological patterns: a pushing pattern, a replacement pattern, and a desmoplastic pattern. The objective of the current study was to explore the prognostic significance of these three growth patterns for survival. The study included 217....... Eventually, the growth patterns may contribute to a histology-based prognostic biomarker for patients with colorectal liver metastases.Modern Pathology advance online publication, 23 May 2014; doi:10.1038/modpathol.2014.4....

  20. Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target

    Science.gov (United States)

    2016-06-01

    AWARD NUMBER: W81XWH-14-1-0107 TITLE: Tumor Microenvironment Gene Signature as a Prognostic Classifier and Therapeutic Target PRINCIPAL...AND SUBTITLE Tumor Microenvironment Gene Signature as a 5a. CONTRACT NUMBER W81XWH-14-1-0107 Prognostic Classifier and Therapeutic Target 5b...gene signature that correlates with poor survival in ovarian cancer patients. We are refining this gene signature to develop biomarkers for the

  1. Biomarkers in pancreatic adenocarcinoma: current perspectives.

    Science.gov (United States)

    Swords, Douglas S; Firpo, Matthew A; Scaife, Courtney L; Mulvihill, Sean J

    2016-01-01

    Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9), which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA), CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC.

  2. Searching for new biomarkers in ovarian cancer patients

    DEFF Research Database (Denmark)

    Hentze, Julie L.; Høgdall, Claus; Kjær, Susanne K.

    2017-01-01

    , by predicting which patients will benefit from specific treatment strategies. The Mermaid III project is consisting of 3 parts including “Early detection, screening and long-term survival,” “Biomarkers and/or prognostic markers” and “The infection theory.” The present paper gives an overview of the part...

  3. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis

    Directory of Open Access Journals (Sweden)

    Stefania Battista

    2016-01-01

    Full Text Available The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism. Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L, calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

  4. Assessment of Diagnostic and Prognostic Role of Copeptin in the Clinical Setting of Sepsis.

    Science.gov (United States)

    Battista, Stefania; Audisio, Umberto; Galluzzo, Claudia; Maggiorotto, Matteo; Masoero, Monica; Forno, Daniela; Pizzolato, Elisa; Ulla, Marco; Lucchiari, Manuela; Vitale, Annarita; Moiraghi, Corrado; Lupia, Enrico; Settanni, Fabio; Mengozzi, Giulio

    2016-01-01

    The diagnostic and prognostic usefulness of copeptin were evaluated in septic patients, as compared to procalcitonin assessment. In this single centre and observational study 105 patients were enrolled: 24 with sepsis, 25 with severe sepsis, 15 with septic shock, and 41 controls, divided in two subgroups (15 patients with gastrointestinal bleeding and 26 with suspected SIRS secondary to trauma, acute coronary syndrome, and pulmonary embolism). Biomarkers were determined at the first medical evaluation and thereafter 24, 48, and 72 hours after admission. Definitive diagnosis and in-hospital survival rates at 30 days were obtained through analysis of medical records. At entry, copeptin proved to be able to distinguish cases from controls and also sepsis group from septic shock group, while procalcitonin could distinguish also severe sepsis from septic shock group. Areas under the ROC curve for copeptin and procalcitonin were 0.845 and 0.861, respectively. Noteworthy, patients with copeptin concentrations higher than the threshold value (23.2 pmol/L), calculated from the ROC curve, at admission presented higher 30-day mortality. No significant differences were found in copeptin temporal profile among different subgroups. Copeptin showed promising diagnostic and prognostic role in the management of sepsis, together with its possible role in monitoring the response to treatment.

  5. Prognostics of Power MOSFET

    Science.gov (United States)

    Celaya, Jose Ramon; Saxena, Abhinav; Vashchenko, Vladislay; Saha, Sankalita; Goebel, Kai Frank

    2011-01-01

    This paper demonstrates how to apply prognostics to power MOSFETs (metal oxide field effect transistor). The methodology uses thermal cycling to age devices and Gaussian process regression to perform prognostics. The approach is validated with experiments on 100V power MOSFETs. The failure mechanism for the stress conditions is determined to be die-attachment degradation. Change in ON-state resistance is used as a precursor of failure due to its dependence on junction temperature. The experimental data is augmented with a finite element analysis simulation that is based on a two-transistor model. The simulation assists in the interpretation of the degradation phenomena and SOA (safe operation area) change.

  6. Biomarkers for Wilms Tumor: a Systematic Review

    Science.gov (United States)

    Cone, Eugene B.; Dalton, Stewart S.; Van Noord, Megan; Tracy, Elizabeth T.; Rice, Henry E.; Routh, Jonathan C.

    2016-01-01

    Purpose Wilms tumor is the most common childhood renal malignancy and the fourth most common childhood cancer. Many biomarkers have been studied but there has been no comprehensive summary. We systematically reviewed the literature on biomarkers in Wilms Tumor with the objective of quantifying the prognostic implication of the presence of individual tumor markers. Methods We searched for English language studies from 1980–2015 performed on children with Wilms Tumor under 18 years old with prognostic data. The protocol was conducted as per PRISMA guidelines. Two reviewers abstracted data in duplicate using a standard evaluation form. We performed descriptive statistics, then calculated relative risks and 95% confidence intervals for markers appearing in multiple level 2 or 3 studies. Results 40 studies were included examining 32 biomarkers in 7381 Wilms patients. Studies had a median of 61 patients with 24 biomarker positive patients per study, and a median follow-up of 68.4 months. Median percent of patients in Stage 1, 2, 3, 4, and 5 were 28.5%, 26.4%, 24.5%, 14.1%, and 1.7%, with 10.2% anaplasia. The strongest negative prognostic association was loss of heterozygosity on 11p15, with a risk of recurrence of 5.00, although loss of heterozygosity on 1p and gain of function on 1q were also strongly linked to increased recurrence (2.93 and 2.86 respectively). Conclusions Several tumor markers are associated with an increased risk of recurrence or a decreased risk of overall survival in Wilms Tumor. These data suggest targets for development of diagnostic tests and potential therapies. PMID:27259655

  7. Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

    Science.gov (United States)

    Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

    2017-06-01

    The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

  8. Prognostic factors in oligodendrogliomas

    DEFF Research Database (Denmark)

    Westergaard, L; Gjerris, F; Klinken, L

    1997-01-01

    An outcome analysis was performed on 96 patients with pure cerebral oligodendrogliomas operated in the 30-year period 1962 to 1991. The most important predictive prognostic factors were youth and no neurological deficit, demonstrated as a median survival for the group younger than 20 years of 17...

  9. Risk prediction in stable cardiovascular disease using a high-sensitivity cardiac troponin T single biomarker strategy compared to the ESC-SCORE.

    Science.gov (United States)

    Biener, Moritz; Giannitsis, Evangelos; Kuhner, Manuel; Zelniker, Thomas; Mueller-Hennessen, Matthias; Vafaie, Mehrshad; Stoyanov, Kiril M; Neumann, Franz-Josef; Katus, Hugo A; Hochholzer, Willibald; Valina, Christian Marc

    2018-01-01

    To evaluate the prognostic performance of high-sensitivity cardiac troponin T (hs-cTnT) compared with the ESC-SCORE. We included low-risk outpatients with stable cardiovascular (CV) disease categorised into need for non-secondary and secondary prevention. The prognostication of hs-cTnT at index visit was compared with the European Society of Cardiology-Systematic COronary Risk Evaluation (ESC-SCORE) with respect to all-cause mortality (ACM) and two composite endpoints (ACM, acute myocardial infarction (AMI) and stroke and ACM, AMI, stroke and rehospitalisation for acute coronary syndrome (ACS) and decompensated heart failure (DHF)). Within a median follow-up of 796 days, a total of 16 deaths, 32 composite endpoints of ACM, AMI and stroke and 83 composite endpoints of ACM, AMI, stroke, rehospitalisation for ACS and DHF were observed among 693 stable low-risk outpatients. Using C-statistics, measurement of hs-cTnT alone outperformed the ESC-SCORE for the prediction of ACM in the entire study population (Δarea under the curve (AUC) 0.221, p=0.0039) and both prevention groups (non-secondary: ΔAUC 0.164, p=0.0208; secondary: ΔAUC 0.264, p=0.0134). For the prediction of all other secondary endpoints, hs-cTnT was at least as effective as the ESC-SCORE, both in secondary and non-secondary prevention. Using continuous and categorical net reclassification improvement and integrated discrimination improvement, hs-cTnT significantly improved reclassification regarding all endpoints in the entire population and in the secondary prevention cohort. In non-secondary prevention, hs-cTnT improved reclassification only for ACM. The results were confirmed in an independent external cohort on 2046 patients. Hs-cTnT is superior to the multivariable ESC-SCORE for the prediction of ACM and a composite endpoint in stable outpatients with and without relevant CV disease. NCT01954303; Pre-results.

  10. Characterization of potential ionizing radiation biomarkers by a proteomic approach

    Energy Technology Data Exchange (ETDEWEB)

    Guipaud, O; Vereycken-Holler, V; Benderitter, M [Institut de Radioprotection et de Surete Nucleaire, Lab. de Radiopathologie, 92 - Fontenay aux Roses (France); Royer, N; Vinh, J [Ecole Superieure de Physique et de Chimie Industrielles, 75 - Paris (France)

    2006-07-01

    Radio-induced lesions are tissue specific, hardly predictable, and can arise months or years later. The finding of prognostic bio-markers is of fundamental relevance for the settlement of therapeutic or preventive strategies. Using two-dimensional gel electrophoresis and mass spectrometry, a proteomic study was applied to look for differentially expressed proteins, i.e. potential bio-markers candidates, in mouse serums after a local irradiation of the dorsal skin. Our results clearly indicated that serum protein content was dynamically modified after a local skin irradiation. A set of specific proteins were early down- or up-regulated and could turn out to be good candidates as diagnostic or prognostic bio-markers. (author)

  11. Characterization of potential ionizing radiation biomarkers by a proteomic approach

    International Nuclear Information System (INIS)

    Guipaud, O.; Vereycken-Holler, V.; Benderitter, M.; Royer, N.; Vinh, J.

    2006-01-01

    Radio-induced lesions are tissue specific, hardly predictable, and can arise months or years later. The finding of prognostic bio-markers is of fundamental relevance for the settlement of therapeutic or preventive strategies. Using two-dimensional gel electrophoresis and mass spectrometry, a proteomic study was applied to look for differentially expressed proteins, i.e. potential bio-markers candidates, in mouse serums after a local irradiation of the dorsal skin. Our results clearly indicated that serum protein content was dynamically modified after a local skin irradiation. A set of specific proteins were early down- or up-regulated and could turn out to be good candidates as diagnostic or prognostic bio-markers. (author)

  12. Mid-regional pro-adrenomedullin as a prognostic marker in sepsis: an observational study

    OpenAIRE

    Christ-Crain, Mirjam; Morgenthaler, Nils G; Struck, Joachim; Harbarth, Stephan; Bergmann, Andreas; Müller, Beat

    2005-01-01

    Introduction Measurement of biomarkers is a potential approach to early assessment and prediction of mortality in patients with sepsis. The aim of the present study was to evaluate the prognostic value of mid-regional pro-adrenomedullin (MR-proADM) levels in a cohort of medical intensive care patients and to compare it with other biomarkers and physiological scores. Method We evaluated blood samples from 101 consecutive critically ill patients admitted to the intensive care unit and from 160 ...

  13. Mining biomarker information in biomedical literature

    Directory of Open Access Journals (Sweden)

    Younesi Erfan

    2012-12-01

    Full Text Available Abstract Background For selection and evaluation of potential biomarkers, inclusion of already published information is of utmost importance. In spite of significant advancements in text- and data-mining techniques, the vast knowledge space of biomarkers in biomedical text has remained unexplored. Existing named entity recognition approaches are not sufficiently selective for the retrieval of biomarker information from the literature. The purpose of this study was to identify textual features that enhance the effectiveness of biomarker information retrieval for different indication areas and diverse end user perspectives. Methods A biomarker terminology was created and further organized into six concept classes. Performance of this terminology was optimized towards balanced selectivity and specificity. The information retrieval performance using the biomarker terminology was evaluated based on various combinations of the terminology's six classes. Further validation of these results was performed on two independent corpora representing two different neurodegenerative diseases. Results The current state of the biomarker terminology contains 119 entity classes supported by 1890 different synonyms. The result of information retrieval shows improved retrieval rate of informative abstracts, which is achieved by including clinical management terms and evidence of gene/protein alterations (e.g. gene/protein expression status or certain polymorphisms in combination with disease and gene name recognition. When additional filtering through other classes (e.g. diagnostic or prognostic methods is applied, the typical high number of unspecific search results is significantly reduced. The evaluation results suggest that this approach enables the automated identification of biomarker information in the literature. A demo version of the search engine SCAIView, including the biomarker retrieval, is made available to the public through http

  14. Serum amyloid A as a prognostic marker in melanoma identified by proteomic profiling.

    Science.gov (United States)

    Findeisen, Peter; Zapatka, Marc; Peccerella, Teresa; Matzk, Heike; Neumaier, Michael; Schadendorf, Dirk; Ugurel, Selma

    2009-05-01

    Currently known prognostic serum biomarkers of melanoma are powerful in metastatic disease, but weak in early-stage patients. This study was aimed to identify new prognostic biomarkers of melanoma by serum mass spectrometry (MS) proteomic profiling, and to validate candidates compared with established markers. Two independent sets of serum samples from 596 melanoma patients were investigated. The first set (stage I = 102; stage IV = 95) was analyzed by matrix assisted laser desorption and ionization time of flight (MALDI TOF) MS for biomarkers differentiating between stage I and IV. In the second set (stage I = 98; stage II = 91; stage III = 87; stage IV = 103), the serum concentrations of the candidate marker serum amyloid A (SAA) and the known biomarkers S100B, lactate dehydrogenase, and C reactive protein (CRP) were measured using immunoassays. MALDI TOF MS revealed a peak at m/z 11.680 differentiating between stage I and IV, which could be identified as SAA. High peak intensities at m/z 11.680 correlated with poor survival. In univariate analysis, SAA was a strong prognostic marker in stage I to III (P = .043) and stage IV (P = .000083) patients. Combination of SAA and CRP increased the prognostic impact to P = .011 in early-stage (I to III) patients. Multivariate analysis revealed sex, stage, tumor load, S100B, SAA, and CRP as independent prognostic factors, with an interaction between SAA and CRP. In stage I to III patients, SAA combined with CRP was superior to S100B in predicting patients' progression-free and overall survival. SAA combined with CRP might be used as prognostic serological biomarkers in early-stage melanoma patients, helping to discriminate low-risk patients from high-risk patients needing adjuvant treatment.

  15. The use of prognostic factors in metastatic renal cell carcinoma.

    Science.gov (United States)

    Li, Haoran; Samawi, Haider; Heng, Daniel Y C

    2015-12-01

    Over the last decade, the treatment landscape of metastatic renal cell carcinoma (mRCC) has evolved tremendously. The outcome of patients with mRCC has been improved since the advent of targeted therapy. In this review, we address the use of prognostic schema in the era of targeted treatment. This article summarizes the current available prognostic models and the evidence to support their use in clinical settings. Prognostic models can help guide clinicians in their decision making, as they have been validated in the first- and second-line targeted therapy settings as well as in non-clear cell mRCC. Prognostic factors are important in patient counseling, clinical trial stratification, and therapy planning. Very selected favorable-risk patients with minimal bulk and slow-growing disease could potentially be observed before needing treatment. Patients with poor-risk disease may be eligible for treatment with temsirolimus. Patients with a very poor prognosis may not be suitable candidates for cytoreductive nephrectomy. New biomarkers are on the horizon, though their roles need to be validated and their additive contribution to improve existing prognostic models examined. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Assessed and Emerging Biomarkers in Stroke and Training-Mediated Stroke Recovery: State of the Art

    Directory of Open Access Journals (Sweden)

    Marialuisa Gandolfi

    2017-01-01

    Full Text Available Since the increasing update of the biomolecular scientific literature, biomarkers in stroke have reached an outstanding and remarkable revision in the very recent years. Besides the diagnostic and prognostic role of some inflammatory markers, many further molecules and biological factors have been added to the list, including tissue derived cytokines, growth factor-like molecules, hormones, and microRNAs. The literatures on brain derived growth factor and other neuroimmune mediators, bone-skeletal muscle biomarkers, cellular and immunity biomarkers, and the role of microRNAs in stroke recovery were reviewed. To date, biomarkers represent a possible challenge in the diagnostic and prognostic evaluation of stroke onset, pathogenesis, and recovery. Many molecules are still under investigation and may become promising and encouraging biomarkers. Experimental and clinical research should increase this list and promote new discoveries in this field, to improve stroke diagnosis and treatment.

  17. A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic Biomarker and Novel Therapeutic Mitochondrial Target

    Science.gov (United States)

    2017-10-01

    goal of this application is to identify targets for the treatment of androgen receptor null castration-resistant prostate cancer in in vitro and pre...AWARD NUMBER: W81XWH-16-1-0584 TITLE : A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic...Missense Mutation in 77% of Prostate Cancer Bone Metastases: 5a. CONTRACT NUMBER A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases

  18. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    Energy Technology Data Exchange (ETDEWEB)

    Bradshaw, Tyler J. [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bowen, Stephen R. [Departments of Radiation Oncology and Radiology, University of Washington, Seattle, Washington (United States); Deveau, Michael A. [Department of Small Animal Clinical Sciences, Texas A& M University, College Station, Texas (United States); Kubicek, Lyndsay [Angell Animal Medical Center, Boston, Massachusetts (United States); White, Pamela [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Bentzen, Søren M. [Division of Biostatistics and Bioinformatics, University of Maryland Greenebaum Cancer Center, and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland (United States); Chappell, Richard J. [Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Forrest, Lisa J. [Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, Wisconsin (United States); Jeraj, Robert, E-mail: rjeraj@wisc.edu [Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States); Department of Human Oncology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin (United States)

    2015-03-15

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV{sub max}; SUV{sub mean}) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R{sup 2}. Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV{sub mean} (P=.018), and midtreatment FLT SUV{sub max} (P=.006). Large decreases in FLT SUV{sub mean} from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV{sub max} (P=.022) in

  19. Molecular Imaging Biomarkers of Resistance to Radiation Therapy for Spontaneous Nasal Tumors in Canines

    International Nuclear Information System (INIS)

    Bradshaw, Tyler J.; Bowen, Stephen R.; Deveau, Michael A.; Kubicek, Lyndsay; White, Pamela; Bentzen, Søren M.; Chappell, Richard J.; Forrest, Lisa J.; Jeraj, Robert

    2015-01-01

    Purpose: Imaging biomarkers of resistance to radiation therapy can inform and guide treatment management. Most studies have so far focused on assessing a single imaging biomarker. The goal of this study was to explore a number of different molecular imaging biomarkers as surrogates of resistance to radiation therapy. Methods and Materials: Twenty-two canine patients with spontaneous sinonasal tumors were treated with accelerated hypofractionated radiation therapy, receiving either 10 fractions of 4.2 Gy each or 10 fractions of 5.0 Gy each to the gross tumor volume. Patients underwent fluorodeoxyglucose (FDG)-, fluorothymidine (FLT)-, and Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (Cu-ATSM)-labeled positron emission tomography/computed tomography (PET/CT) imaging before therapy and FLT and Cu-ATSM PET/CT imaging during therapy. In addition to conventional maximum and mean standardized uptake values (SUV max ; SUV mean ) measurements, imaging metrics providing response and spatiotemporal information were extracted for each patient. Progression-free survival was assessed according to response evaluation criteria in solid tumor. The prognostic value of each imaging biomarker was evaluated using univariable Cox proportional hazards regression. Multivariable analysis was also performed but was restricted to 2 predictor variables due to the limited number of patients. The best bivariable model was selected according to pseudo-R 2 . Results: The following variables were significantly associated with poor clinical outcome following radiation therapy according to univariable analysis: tumor volume (P=.011), midtreatment FLT SUV mean (P=.018), and midtreatment FLT SUV max (P=.006). Large decreases in FLT SUV mean from pretreatment to midtreatment were associated with worse clinical outcome (P=.013). In the bivariable model, the best 2-variable combination for predicting poor outcome was high midtreatment FLT SUV max (P=.022) in combination with large FLT response from

  20. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor

    DEFF Research Database (Denmark)

    Hansen, Torben Frøstrup; Spindler, Karen-Lise Garm; Andersen, Rikke Fredslund

    2010-01-01

    Abstract: New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study...... using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible...... findings in a second and independent cohort. Haplotype combinations call for further investigation. Keywords: colorectal neoplasm; single nucleotide polymorphisms; haplotypes; vascular endothelial growth factor A; survival...

  1. MICRONUCLEI: A PROGNOSTIC TOOL

    OpenAIRE

    Ankit; Rinky; Manisha; Sonalika; Anand; Sanyog

    2014-01-01

    Squamous cell carcinoma is one the most common oral mucosal malignant tumor, diagnosis of oral squamous cell carcinoma rarely presents difficulty, it is the cancer staging and histo pathological grading that are more important for prognosis, micronuclei are good prognostic indicator. Micronuclei screening can be done easily by exfoliative cytology, one of the most valuable diagnostic method other than routine histopathology (H and E-stained sections) and immunohistochemist...

  2. A molecular prognostic model predicts esophageal squamous cell carcinoma prognosis.

    Directory of Open Access Journals (Sweden)

    Hui-Hui Cao

    Full Text Available Esophageal squamous cell carcinoma (ESCC has the highest mortality rates in China. The 5-year survival rate of ESCC remains dismal despite improvements in treatments such as surgical resection and adjuvant chemoradiation, and current clinical staging approaches are limited in their ability to effectively stratify patients for treatment options. The aim of the present study, therefore, was to develop an immunohistochemistry-based prognostic model to improve clinical risk assessment for patients with ESCC.We developed a molecular prognostic model based on the combined expression of axis of epidermal growth factor receptor (EGFR, phosphorylated Specificity protein 1 (p-Sp1, and Fascin proteins. The presence of this prognostic model and associated clinical outcomes were analyzed for 130 formalin-fixed, paraffin-embedded esophageal curative resection specimens (generation dataset and validated using an independent cohort of 185 specimens (validation dataset.The expression of these three genes at the protein level was used to build a molecular prognostic model that was highly predictive of ESCC survival in both generation and validation datasets (P = 0.001. Regression analysis showed that this molecular prognostic model was strongly and independently predictive of overall survival (hazard ratio = 2.358 [95% CI, 1.391-3.996], P = 0.001 in generation dataset; hazard ratio = 1.990 [95% CI, 1.256-3.154], P = 0.003 in validation dataset. Furthermore, the predictive ability of these 3 biomarkers in combination was more robust than that of each individual biomarker.This technically simple immunohistochemistry-based molecular model accurately predicts ESCC patient survival and thus could serve as a complement to current clinical risk stratification approaches.

  3. Clinical Risk Stratification Optimizes Value of Biomarkers to Predict New-Onset Heart Failure in a Community-Based Cohort

    NARCIS (Netherlands)

    Brouwers, Frank P.; van Gilst, Wiek H.; Damman, Kevin; van den Berg, Maarten P.; Gansevoort, Ron T.; Bakker, Stephan J. L.; Hillege, Hans L.; van Veldhuisen, Dirk J.; van der Harst, Pim; de Boer, Rudolf A.

    Background-We aim to identify and quantify the value of biomarkers for incident new-onset heart failure (HF) in a community-based cohort and subgroups based on cardiovascular risk and evaluate the prognostic value of 13 biomarkers for HF with reduced and preserved ejection fraction. Methods and

  4. Clinical Correlates and Prognostic Value of Proenkephalin in Acute and Chronic Heart Failure

    NARCIS (Netherlands)

    Matsue, Yuya; ter Maaten, Jozine M.; Struck, Joachim; Metra, Marco; O'Connor, Christopher M.; Ponikowski, Piotr; Teerlink, John R.; Cotter, Gad; Davison, Beth; Cleland, John G.; Givertz, Michael M.; Bloomfield, Daniel M.; Dittrich, Howard C.; van Veldhuisen, Dirk J.; van der Meer, Peter; Damman, Kevin; Voors, Adriaan A.

    Background: Proenkephalin (pro-ENK) has emerged as a novel biomarker associated with both renal function and cardiac function. However, its clinical and prognostic value have not been well evaluated in symptomatic patients with heart failure. Methods and Results: The association between pro-ENK and

  5. Consensus definitions and application guidelines for control groups in cerebrospinal fluid biomarker studies in multiple sclerosis

    DEFF Research Database (Denmark)

    Teunissen, Charlotte; Menge, Til; Altintas, Ayse

    2013-01-01

    The choice of appropriate control group(s) is critical in cerebrospinal fluid (CSF) biomarker research in multiple sclerosis (MS). There is a lack of definitions and nomenclature of different control groups and a rationalized application of different control groups. We here propose consensus......). Furthermore, we discuss the application of these control groups in specific study designs, such as for diagnostic biomarker studies, prognostic biomarker studies and therapeutic response studies. Application of these uniform definitions will lead to better comparability of biomarker studies and optimal use...

  6. The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma

    Energy Technology Data Exchange (ETDEWEB)

    Hoejklint Poulsen, Sidsel [The Finsen Center, Rigshospitalet, Department of Radiation Biology, Copenhagen (Denmark); Center of Diagnostic Investigation, Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); Urup, Thomas; Grunnet, Kirsten; Skovgaard Poulsen, Hans [The Finsen Center, Rigshospitalet, Department of Radiation Biology, Copenhagen (Denmark); The Finsen Center, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); Jarle Christensen, Ib [University of Copenhagen, Hvidovre Hospital, Laboratory of Gastroenterology, Copenhagen (Denmark); Larsen, Vibeke Andree [Center of Diagnostic Investigation, Rigshospitalet, Department of Radiology, Copenhagen (Denmark); Lundemann Jensen, Michael; Munck af Rosenschoeld, Per [The Finsen Center, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); The Finsen Center, Rigshospitalet, Section of Radiotherapy, Copenhagen (Denmark); Law, Ian [Center of Diagnostic Investigation, Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark)

    2017-03-15

    Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-{sup 18}F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker. We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV). Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors. Large BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning. (orig.)

  7. Prognostic factors of breast cancer

    International Nuclear Information System (INIS)

    Gonzalez Ortega, Jose Maria; Morales Wong, Mario Miguel; Lopez Cuevas, Zoraida; Diaz Valdez, Marilin

    2011-01-01

    The prognostic factors must to be differentiated of the predictive ones. A prognostic factor is any measurement used at moment of the surgery correlated with the free interval of disease or global survival in the absence of the systemic adjuvant treatment and as result is able to correlate with the natural history of the disease. In contrast, a predictive factor is any measurement associated with the response to a given treatment. Among the prognostic factors of the breast cancer are included the clinical, histological, biological, genetic and psychosocial factors. In present review of psychosocial prognostic factors has been demonstrated that the stress and the depression are negative prognostic factors in patients presenting with breast cancer. It is essential to remember that the assessment of just one prognostic parameter is a help but it is not useful to clinical and therapeutic management of the patient.(author)

  8. Prognostic Stratification of Patients With Advanced Oral Cavity Squamous Cell Carcinoma.

    Science.gov (United States)

    De Paz, Dante; Kao, Huang-Kai; Huang, Yenlin; Chang, Kai-Ping

    2017-08-10

    Prognosis of advanced oral squamous cell carcinoma remains a challenge for clinicians despite progress in its diagnosis and treatment over the past decades. In this review, we assessed clinicopathological factors and potential biomarkers along with their prognostic relevance in an attempt to develop optimal treatment strategies for these patients. In addition to several pathologic factors that have been proposed to improve prognostic stratification and treatment planning in the eighth edition of the American Joint Committee staging manual on cancer, we reviewed some other imaging and clinicopathological parameters demonstrated to be closely associated with patient prognosis, along with the biomarkers related to novel target or immune therapy. Evaluation of current literature regarding the prognostic stratification used in contemporary clinicopathological studies and progress in the development of targeted or immune therapy may help these patients benefit from tailored and personalized treatment and obtain better oncological results.

  9. Cardiovascular biomarkers and sex: the case for women.

    Science.gov (United States)

    Daniels, Lori B; Maisel, Alan S

    2015-10-01

    Measurement of biomarkers is a critical component of cardiovascular care. Women and men differ in their cardiac physiology and manifestations of cardiovascular disease. Although most cardiovascular biomarkers are used by clinicians without taking sex into account, sex-specific differences in biomarkers clearly exist. Baseline concentrations of many biomarkers (including cardiac troponin, natriuretic peptides, galectin-3, and soluble ST2) differ in men versus women, but these sex-specific differences do not generally translate into a need for differential sex-based cut-off points. Furthermore, most biomarkers are similarly diagnostic and prognostic, regardless of sex. Two potential exceptions are cardiac troponins measured by high-sensitivity assay, and proneurotensin. Troponin levels are lower in women than in men and, with the use of high-sensitivity assays, sex-specific cut-off points might improve the diagnosis of myocardial infarction. Proneurotensin is a novel biomarker that was found to be predictive of incident cardiovascular disease in women, but not men, and was also predictive of incident breast cancer. If confirmed, proneurotensin might be a unique biomarker of disease risk in women. With any biomarker, an understanding of sex-specific differences might improve its use and might also lead to an enhanced understanding of the physiological differences between the hearts of men and women.

  10. Clinical Relevance of Prognostic and Predictive Molecular Markers in Gliomas.

    Science.gov (United States)

    Siegal, Tali

    2016-01-01

    Sorting and grading of glial tumors by the WHO classification provide clinicians with guidance as to the predicted course of the disease and choice of treatment. Nonetheless, histologically identical tumors may have very different outcome and response to treatment. Molecular markers that carry both diagnostic and prognostic information add useful tools to traditional classification by redefining tumor subtypes within each WHO category. Therefore, molecular markers have become an integral part of tumor assessment in modern neuro-oncology and biomarker status now guides clinical decisions in some subtypes of gliomas. The routine assessment of IDH status improves histological diagnostic accuracy by differentiating diffuse glioma from reactive gliosis. It carries a favorable prognostic implication for all glial tumors and it is predictive for chemotherapeutic response in anaplastic oligodendrogliomas with codeletion of 1p/19q chromosomes. Glial tumors that contain chromosomal codeletion of 1p/19q are defined as tumors of oligodendroglial lineage and have favorable prognosis. MGMT promoter methylation is a favorable prognostic marker in astrocytic high-grade gliomas and it is predictive for chemotherapeutic response in anaplastic gliomas with wild-type IDH1/2 and in glioblastoma of the elderly. The clinical implication of other molecular markers of gliomas like mutations of EGFR and ATRX genes and BRAF fusion or point mutation is highlighted. The potential of molecular biomarker-based classification to guide future therapeutic approach is discussed and accentuated.

  11. Prognostic impact of hemoglobin level and other factors in patients with high-grade gliomas treated with postoperative radiochemotherapy and sequential chemotherapy based on temozolomide. A 10-year experience at a single institution

    International Nuclear Information System (INIS)

    Ausili Cefaro, Giampiero; Genovesi, Domenico; Vinciguerra, Annamaria; Trignani, Marianna; Taraborrelli, Maria; Augurio, Antonietta; Buonaguidi, Roberto; Galzio, Renato J.; Di Nicola, Marta

    2011-01-01

    To evaluate the influence of serum hemoglobin level prior to radiotherapy and other prognostic factors on survival in patients with high-grade gliomas. From 2001-2010, we retrospectively evaluated a total of 48 patients with malignant glioma treated with surgery and postoperative radiochemotherapy with temozolomide. A total of 37 of 48 patients received sequential temozolomide. Hemoglobin levels were assayed before radiotherapy in all patients. The Kaplan-Meier method was applied to estimate the overall survival, while the log-rank test was applied to evaluate the differences on survival probability between prognostic subgroups. Results were assessed in 43 patients. The median overall survival time was 18 months (95% confidence interval: 12-40 months). The 1- and 2-year survival rates were 62.2% and 36.3%, respectively. The prognostic factors analyzed were gender, age, extent of surgery, performance status before and after radiotherapy, sequential chemotherapy, hemoglobin level, and methylation of the O-6-methylguanine-DNA methyltransferase gene (MGMT). In univariate analysis, the variables significantly related to survival were performance status before and after radiotherapy, sequential chemotherapy, and hemoglobin level. The median overall survival in patients with a hemoglobin level ≤ 12 g/dl was 12 months and 23 months in patients with a hemoglobin level > 12 g/dl. The 1- and 2-year survival rates were 46.7% and 20.0%, respectively, for patients with a hemoglobin level ≤ 12 mg/dl and 69.6% and 45.7%, respectively, for patients with a hemoglobin level > 12 g/dl. Our results confirm the impact of well-known prognostic factors on survival. In this research, it was found that a low hemoglobin level before radiotherapy can adversely influence the prognosis of patients with malignant gliomas.

  12. Functional, Structural, and Neurotoxicity Biomarkers in Integrative Assessment of Concussions

    Directory of Open Access Journals (Sweden)

    Svetlana A Dambinova

    2016-10-01

    Full Text Available Concussion is a complex, heterogenous process affecting the brain. Accurate assessment and diagnosis and appropriate management of concussion are essential to ensure athletes do not prematurely return to play or others to work or active military duty, risking re-injury. To date, clinical diagnosis relies primarily on evaluating subjects for functional impairment using instruments that include neurocognitive testing, subjective symptom report, and neurobehavioral assessments, such as balance and vestibular-ocular reflex testing. Structural biomarkers, defined as advanced neuroimaging techniques and biomarkers assessing neurotoxicity and immunoexcitotoxicity may complement the use of functional biomarkers. We hypothesize that neurotoxicity AMPA, NMDA, and kainite receptor biomarkers might be utilized as a part of comprehensive approach to concussion evaluations, with the goal of increasing diagnostic accuracy and facilitating treatment planning and prognostic assessment.

  13. Biomarkers for Lupus Nephritis: A Critical Appraisal

    Directory of Open Access Journals (Sweden)

    Chi Chiu Mok

    2010-01-01

    Full Text Available Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE. Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Besides exploring more effective but less toxic treatment modalities that will further improve the remission rate, early detection and treatment of renal activity may spare patients from intensive immunosuppressive therapies and reduce renal damage. Conventional clinical parameters such as creatinine clearance, proteinuria, urine sediments, anti-dsDNA, and complement levels are not sensitive or specific enough for detecting ongoing disease activity in the lupus kidneys and early relapse of nephritis. Thus, novel biomarkers are necessary to enhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response, and detection of early renal flares. This paper reviews promising biomarkers that have recently been evaluated in longitudinal studies of lupus nephritis.

  14. Combination of biomarkers

    DEFF Research Database (Denmark)

    Thurfjell, Lennart; Lötjönen, Jyrki; Lundqvist, Roger

    2012-01-01

    The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury.......The New National Institute on Aging-Alzheimer's Association diagnostic guidelines for Alzheimer's disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury....

  15. Evaluation of breast cancer using intravoxel incoherent motion (IVIM) histogram analysis: comparison with malignant status, histological subtype, and molecular prognostic factors.

    Science.gov (United States)

    Cho, Gene Young; Moy, Linda; Kim, Sungheon G; Baete, Steven H; Moccaldi, Melanie; Babb, James S; Sodickson, Daniel K; Sigmund, Eric E

    2016-08-01

    To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44 ± 11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann-Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman's rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients. • Novel IVIM biomarkers characterize heterogeneous breast cancer. • Histogram analysis enables quantification of tumour heterogeneity. • IVIM biomarkers show relationships with breast cancer malignancy and molecular prognostic factors.

  16. Rapid label-free profiling of oral cancer biomarker proteins using nano-UPLC-Q-TOF ion mobility mass spectrometry.

    Science.gov (United States)

    Nassar, Ala F; Williams, Brad J; Yaworksy, Dustin C; Patel, Vyomesh; Rusling, James F

    2016-03-01

    It has become quite clear that single cancer biomarkers cannot in general provide high sensitivity and specificity for reliable clinical cancer diagnostics. This paper explores the feasibility of rapid detection of multiple biomarker proteins in model oral cancer samples using label-free protein relative quantitation. MS-based label-free quantitative proteomics offer a rapid alternative that bypasses the need for stable isotope containing compounds to chemically bind and label proteins. Total protein content in oral cancer cell culture conditioned media was precipitated, subjected to proteolytic digestion, and then analyzed using a nano-UPLC (where UPLC is ultra-performance liquid chromatography) coupled to a hybrid Q-Tof ion-mobility mass spectrometry (MS). Rapid, simultaneous identification and quantification of multiple possible cancer biomarker proteins was achieved. In a comparative study between cancer and noncancer samples, approximately 952 proteins were identified using a high-throughput 1D ion mobility assisted data independent acquisition (IM-DIA) approach. As we previously demonstrated that interleukin-8 (IL-8) and vascular endothelial growth factor A (VEGF-A) were readily detected in oral cancer cell conditioned media(1), we targeted these biomarker proteins to validate our approach. Target biomarker protein IL-8 was found between 3.5 and 8.8 fmol, while VEGF-A was found at 1.45 fmol in the cancer cell media. Overall, our data suggest that the nano-UPLC-IM-DIA bioassay is a feasible approach to identify and quantify proteins in complex samples without the need for stable isotope labeling. These results have significant implications for rapid tumor diagnostics and prognostics by monitoring proteins such as IL-8 and VEGF-A implicated in cancer development and progression. The analysis in tissue or plasma is not possible at this time, but the subsequent work would be needed for validation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Biomarkers in pancreatic adenocarcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Swords DS

    2016-12-01

    Full Text Available Douglas S Swords, Matthew A Firpo, Courtney L Scaife, Sean J Mulvihill Department of Surgery, University of Utah Health Sciences, Salt Lake City, UT, USA Abstract: Pancreatic ductal adenocarcinoma (PDAC has a poor prognosis, with a 5-year survival rate of 7.7%. Most patients are diagnosed at an advanced stage not amenable to potentially curative resection. A substantial portion of this review is dedicated to reviewing the current literature on carbohydrate antigen (CA 19-9, which is currently the only guideline-recommended biomarker for PDAC. It provides valuable prognostic information, can predict resectability, and is useful in decision making about neoadjuvant therapy. We also discuss carcinoembryonic antigen (CEA, CA 125, serum biomarker panels, circulating tumor cells, and cell-free nucleic acids. Although many biomarkers have now been studied in relation to PDAC, significant work still needs to be done to validate their usefulness in the early detection of PDAC and management of patients with PDAC. Keywords: pancreatic cancer, biomarkers, screening, CA 19-9, CEA

  18. Interactomic approach for evaluating nucleophosmin-binding proteins as biomarkers for Ewing's sarcoma.

    Science.gov (United States)

    Haga, Ayako; Ogawara, Yoko; Kubota, Daisuke; Kitabayashi, Issay; Murakami, Yasufumi; Kondo, Tadashi

    2013-06-01

    Nucleophosmin (NPM) is a novel prognostic biomarker for Ewing's sarcoma. To evaluate the prognostic utility of NPM, we conducted an interactomic approach to characterize the NPM protein complex in Ewing's sarcoma cells. A gene suppression assay revealed that NPM promoted cell proliferation and the invasive properties of Ewing's sarcoma cells. FLAG-tag-based affinity purification coupled with liquid chromatography-tandem mass spectrometry identified 106 proteins in the NPM protein complex. The functional classification suggested that the NPM complex participates in critical biological events, including ribosome biogenesis, regulation of transcription and translation, and protein folding, that are mediated by these proteins. In addition to JAK1, a candidate prognostic biomarker for Ewing's sarcoma, the NPM complex, includes 11 proteins known as prognostic biomarkers for other malignancies. Meta-analysis of gene expression profiles of 32 patients with Ewing's sarcoma revealed that 6 of 106 were significantly and independently associated with survival period. These observations suggest a functional role as well as prognostic value of these NPM complex proteins in Ewing's sarcoma. Further, our study suggests the potential applications of interactomics in conjunction with meta-analysis for biomarker discovery. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. The Prognostic and Predictive Value of Soluble Type IV Collagen in Colorectal Cancer

    DEFF Research Database (Denmark)

    Rolff, Hans Christian; Christensen, Ib Jarle; Vainer, Ben

    2016-01-01

    PURPOSE: To investigate the prognostic and predictive biomarker value of type IV collagen in colorectal cancer. EXPERIMENTAL DESIGN: Retrospective evaluation of two independent cohorts of patients with colorectal cancer included prospectively in 2004-2005 (training set) and 2006-2008 (validation....... RESULTS: High levels of type IV collagen showed independent prognostic significance in both cohorts with hazard ratios (HRs; for a one-unit change on the log base 2 scale) of 2.25 [95% confidence intervals (CIs), 1.78-2.84; P ... and validation set, respectively. The prognostic impact was present both in patients with metastatic and nonmetastatic disease. The predictive value of the marker was investigated in stage II and III patients. In the training set, type IV collagen was prognostic both in the subsets of patients receiving...

  20. Prognostic factors in lupus nephritis

    DEFF Research Database (Denmark)

    Faurschou, Mikkel; Starklint, Henrik; Halberg, Poul

    2006-01-01

    To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis.......To evaluate the prognostic significance of clinical and renal biopsy findings in an unselected cohort of patients with systemic lupus erythematosus (SLE) and nephritis....

  1. Cross-study and cross-omics comparisons of three nephrotoxic compounds reveal mechanistic insights and new candidate biomarkers

    International Nuclear Information System (INIS)

    Matheis, Katja A.; Com, Emmanuelle; Gautier, Jean-Charles; Guerreiro, Nelson; Brandenburg, Arnd; Gmuender, Hans; Sposny, Alexandra; Hewitt, Philip; Amberg, Alexander; Boernsen, Olaf; Riefke, Bjoern; Hoffmann, Dana; Mally, Angela; Kalkuhl, Arno; Suter, Laura; Dieterle, Frank; Staedtler, Frank

    2011-01-01

    The European InnoMed-PredTox project was a collaborative effort between 15 pharmaceutical companies, 2 small and mid-sized enterprises, and 3 universities with the goal of delivering deeper insights into the molecular mechanisms of kidney and liver toxicity and to identify mechanism-linked diagnostic or prognostic safety biomarker candidates by combining conventional toxicological parameters with 'omics' data. Mechanistic toxicity studies with 16 different compounds, 2 dose levels, and 3 time points were performed in male Crl: WI(Han) rats. Three of the 16 investigated compounds, BI-3 (FP007SE), Gentamicin (FP009SF), and IMM125 (FP013NO), induced kidney proximal tubule damage (PTD). In addition to histopathology and clinical chemistry, transcriptomics microarray and proteomics 2D-DIGE analysis were performed. Data from the three PTD studies were combined for a cross-study and cross-omics meta-analysis of the target organ. The mechanistic interpretation of kidney PTD-associated deregulated transcripts revealed, in addition to previously described kidney damage transcript biomarkers such as KIM-1, CLU and TIMP-1, a number of additional deregulated pathways congruent with histopathology observations on a single animal basis, including a specific effect on the complement system. The identification of new, more specific biomarker candidates for PTD was most successful when transcriptomics data were used. Combining transcriptomics data with proteomics data added extra value.

  2. Prognostic accuracy of antenatal neonatology consultation.

    Science.gov (United States)

    Kukora, S; Gollehon, N; Weiner, G; Laventhal, N

    2017-01-01

    Neonatologists provide antenatal counseling to support shared decision-making for complicated pregnancies. Poor or ambiguous prognostication can lead to inappropriate treatment and parental distress. We sought to evaluate the accuracy of antenatal prognosticaltion. A retrospective cohort was assembled from a prospectively populated database of all outpatient neonatology consultations. On the basis of the written consultation, fetuses were characterized by diagnosis groups (multiple anomalies or genetic disorders, single major anomaly and obstetric complications), assigned to five prognostic categories (I=survivable, IIA=uncertain but likely survivable, II=uncertain, IIB=uncertain but likely non-survivable, III non-survivable) and two final outcome categories (fetal demise/in-hospital neonatal death or survival to hospital discharge). When possible, status at last follow-up was recorded for those discharged from the hospital. Prognostic accuracy was assessed using unweighted, multi-level likelihood ratios (LRs). The final cohort included 143 fetuses/infants distributed nearly evenly among the three diagnosis groups. Over half (64%) were assigned an uncertain prognosis, but most of these could be divided into 'likely survivable' or 'likely non-survivable' subgroups. Overall survival for the entire cohort was 62% (89/143). All but one of the fetuses assigned a non-survivable prognosis suffered fetal demise or died before hospital discharge. The neonatologist's antenatal prognosis accurately predicted the probability of survival by prognosis group (LR I=4.56, LR IIA=10.53, LR II=4.71, LR IIB=0.099, LR III=0.040). The LRs clearly differentiated between fetuses with high and low probability of survival. Eleven fetuses (7.7%) had misalignment between the predicted prognosis and outcome. Five died before discharge despite being given category I or IIA prognoses, whereas six infants with category IIB or III prognoses survived to discharge, though some of these were

  3. Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

    Directory of Open Access Journals (Sweden)

    Luca Arcaini

    2012-01-01

    Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

  4. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-01-01

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments. PMID:26855534

  5. Colorectal cancer tumour markers and biomarkers: Recent therapeutic advances.

    Science.gov (United States)

    Lech, Gustaw; Słotwiński, Robert; Słodkowski, Maciej; Krasnodębski, Ireneusz Wojciech

    2016-02-07

    Colorectal cancer (CRC) is the second most commonly diagnosed cancer among females and third among males worldwide. It also contributes significantly to cancer-related deaths, despite the continuous progress in diagnostic and therapeutic methods. Biomarkers currently play an important role in the detection and treatment of patients with colorectal cancer. Risk stratification for screening might be augmented by finding new biomarkers which alone or as a complement of existing tests might recognize either the predisposition or early stage of the disease. Biomarkers have also the potential to change diagnostic and treatment algorithms by selecting the proper chemotherapeutic drugs across a broad spectrum of patients. There are attempts to personalise chemotherapy based on presence or absence of specific biomarkers. In this review, we update review published last year and describe our understanding of tumour markers and biomarkers role in CRC screening, diagnosis, treatment and follow-up. Goal of future research is to identify those biomarkers that could allow a non-invasive and cost-effective diagnosis, as well as to recognise the best prognostic panel and define the predictive biomarkers for available treatments.

  6. Predictive and Prognostic Factors in Colorectal Cancer: A Personalized Approach

    Directory of Open Access Journals (Sweden)

    Timothy A. Rockall

    2011-03-01

    Full Text Available It is an exciting time for all those engaged in the treatment of colorectal cancer. The advent of new therapies presents the opportunity for a personalized approach to the patient. This approach considers the complex genetic mechanisms involved in tumorigenesis in addition to classical clinicopathological staging. The potential predictive and prognostic biomarkers which have stemmed from the study of the genetic basis of colorectal cancer and therapeutics are discussed with a focus on mismatch repair status, KRAS, BRAF, 18qLOH, CIMP and TGF-β.

  7. Amyotrophic Lateral Sclerosis Multiprotein Biomarkers in Peripheral Blood Mononuclear Cells

    OpenAIRE

    Nardo, Giovanni; Pozzi, Silvia; Pignataro, Mauro; Lauranzano, Eliana; Spano, Giorgia; Garbelli, Silvia; Mantovani, Stefania; Marinou, Kalliopi; Papetti, Laura; Monteforte, Marta; Torri, Valter; Paris, Luca; Bazzoni, Gianfranco; Lunetta, Christian; Corbo, Massimo

    2011-01-01

    Background Amyotrophic lateral sclerosis (ALS) is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments. Methodology/Principal Findings We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC), a panel...

  8. 3D Quantitative tumour burden analysis in patients with hepatocellular carcinoma before TACE: comparing single-lesion vs. multi-lesion imaging biomarkers as predictors of patient survival

    International Nuclear Information System (INIS)

    Fleckenstein, Florian N.; Schernthaner, Ruediger E.; Duran, Rafael; Sohn, Jae Ho; Sahu, Sonia; Zhao, Yan; Hamm, Bernd; Gebauer, Bernhard; Lin, MingDe; Geschwind, Jean-Francois; Chapiro, Julius

    2016-01-01

    To compare the ability of single- vs. multi-lesion assessment on baseline MRI using 1D- and 3D-based measurements to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC) before transarterial chemoembolization (TACE). This retrospective analysis included 122 patients. A quantitative 3D analysis was performed on baseline MRI to calculate enhancing tumour volume (ETV [cm 3 ]) and enhancing tumour burden (ETB [%]) (ratio between ETV [cm 3 ] and liver volume). Furthermore, enhancing and overall tumour diameters were measured. Patients were stratified into two groups using thresholds derived from the BCLC staging system. Statistical analysis included Kaplan-Meier plots, uni- and multivariate cox proportional hazard ratios (HR) and concordances. All methods achieved good separation of the survival curves (p < 0.05). Multivariate analysis showed an HR of 5.2 (95 % CI 3.1-8.8, p < 0.001) for ETV [cm 3 ] and HR 6.6 (95 % CI 3.7-11.5, p < 0.001) for ETB [%] vs. HR 2.6 (95 % CI 1.2-5.6, p = 0.012) for overall diameter and HR 3.0 (95 % CI 1.5-6.3, p = 0.003) for enhancing diameter. Concordances were highest for ETB [%], with no added predictive power for multi-lesion assessment (difference between concordances not significant). 3D quantitative assessment is a stronger predictor of survival as compared to diameter-based measurements. Assessing multiple lesions provides no substantial improvement in predicting OS than evaluating the dominant lesion alone. (orig.)

  9. Colorectal Cancer: Prognostic Values

    Directory of Open Access Journals (Sweden)

    Suzana Manxhuka-Kerliu

    2009-02-01

    Full Text Available After lung cancer colorectal cancer (Cc is ranked the second, as a cause of cancer-related death. The purpose of this study was to analyze the Cc cases in our material with respect to all prognostic values including histological type and grade, vascular invasion, perineural invasion, and tumor border features. There were investigated 149 cases of resection specimen with colorectal cancer, which were fixed in buffered neutral formalin and embedded in paraffin. Tissue sections (4(µm thick were cut and stained with H&E. Adenocarcinoma was the most frequent histological type found in 85,90% of cases, in 60,94% of males and 39,06% of females; squamous cell carcinoma in 7,38%, in 63,63% of males and 36,36% of females; mucinous carcinoma in 4,68%, in 57,15% of males and 42,85% of females; while adenosquamous carcinoma, undifferentiated carcinoma and carcinoma in situ in 0,71% of cases each. Dukes' classification was used in order to define the depth of invasion. Dukes B was found in 68,45% of cases, whereas in 31,54% of cases Dukes C was found. As far as histological grading is concerned, Cc was mostly with moderate differentiation (75,16% with neither vascular nor perineural invasion. Resection margins were in all cases free of tumor. Our data indicate that the pathologic features of the resection specimen constitute the most powerful predictors of postoperative outcome in Cc. Dukes' stage and degree of differentiation provide independent prognostic information in Cc. However, differentiation should be assessed by the worst pattern.

  10. Molecular biomarkers for weight control in obese individuals subjected to a multi-phase dietary intervention

    DEFF Research Database (Denmark)

    Bolton, Jennifer L; Montastier, Emilie; Carayol, Jérôme

    2017-01-01

    Context: While calorie restriction has proven beneficial for weight loss, long-term weight control is variable between individuals. Objective: To identify biomarkers of successful weight control during a dietary intervention (DI). Design, Setting, and Participants: Adipose tissue (AT) transcripto......-controllers. Interestingly, ASPN is a TGFβ1 inhibitor. Conclusions: We found circulating biomarkers associated with weight control, which could influence weight management strategies, and genes that may be prognostic for successful weight control....

  11. The Thoc1 Ribonucleoprotein as a Novel Biomarker for Prostate Cancer Treatment Assignment

    Science.gov (United States)

    2017-10-01

    for prostate cancer , the work may impact development of diagnostic /prognostic products based on pThoc1. The presence of the THO ribonucleoprotin...AWARD NUMBER: W81XWH-14-1-0475 TITLE: The Thoc1 Ribonucleoprotein as a Novel Biomarker for Prostate Cancer Treatment Assignment PRINCIPAL...15Sept 2016 - 14Sep2017 4. TITLE AND SUBTITLE The Thoc1 Ribonucleoprotein as a Novel Biomarker for Prostate 5a. CONTRACT NUMBER Cancer Treatment

  12. Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.

    Directory of Open Access Journals (Sweden)

    Joanna M Lubieniecka

    Full Text Available One of the major challenges in management of spinal cord injury (SCI is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS analyses of cerebrospinal fluid (CSF collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.

  13. Biomarkers for Severity of Spinal Cord Injury in the Cerebrospinal Fluid of Rats

    Science.gov (United States)

    Lubieniecka, Joanna M.; Streijger, Femke; Lee, Jae H. T.; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K.; Coorssen, Jens R.; Foster, Leonard J.; Grigliatti, Thomas A.; Tetzlaff, Wolfram

    2011-01-01

    One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage. PMID:21559420

  14. Early biomarkers of joint damage in rheumatoid and psoriatic arthritis.

    LENUS (Irish Health Repository)

    Mc Ardle, Angela

    2015-01-01

    Joint destruction, as evidenced by radiographic findings, is a significant problem for patients suffering from rheumatoid arthritis and psoriatic arthritis. Inherently irreversible and frequently progressive, the process of joint damage begins at and even before the clinical onset of disease. However, rheumatoid and psoriatic arthropathies are heterogeneous in nature and not all patients progress to joint damage. It is therefore important to identify patients susceptible to joint destruction in order to initiate more aggressive treatment as soon as possible and thereby potentially prevent irreversible joint damage. At the same time, the high cost and potential side effects associated with aggressive treatment mean it is also important not to over treat patients and especially those who, even if left untreated, would not progress to joint destruction. It is therefore clear that a protein biomarker signature that could predict joint damage at an early stage would support more informed clinical decisions on the most appropriate treatment regimens for individual patients. Although many candidate biomarkers for rheumatoid and psoriatic arthritis have been reported in the literature, relatively few have reached clinical use and as a consequence the number of prognostic biomarkers used in rheumatology has remained relatively static for several years. It has become evident that a significant challenge in the transition of biomarker candidates to clinical diagnostic assays lies in the development of suitably robust biomarker assays, especially multiplexed assays, and their clinical validation in appropriate patient sample cohorts. Recent developments in mass spectrometry-based targeted quantitative protein measurements have transformed our ability to rapidly develop multiplexed protein biomarker assays. These advances are likely to have a significant impact on the validation of biomarkers in the future. In this review, we have comprehensively compiled a list of candidate

  15. Biomarkers, Natural Course and Prognosis.

    Science.gov (United States)

    Arenillas, Juan F; López-Cancio, Elena; Wong, Ka Sing

    2016-01-01

    Increasing our knowledge about intracranial atherosclerosis (ICAS) natural history and prognostic factors is essential to improve its preventive therapy and thus reduce the dramatic clinical consequences caused by this entity. ICAS is characterized by a chronic and progressive course until it becomes symptomatic, mostly through complication of an unstable intracranial atherosclerotic plaque. Population-based studies in healthy subjects have shown that the prevalence of asymptomatic ICAS is higher in Asian than in Caucasian populations. In both settings, asymptomatic ICAS is associated with classical vascular risk factors and with the metabolic syndrome, and it is burdened with an increasing risk of having incident stroke and cognitive impairment. When it reaches its symptomatic stage, ICAS is a dynamic and aggressive condition, and affected patients are at high risk of having recurrent stroke and other major vascular events. The Stenting versus Aggressive Medical Therapy for Intracranial Arterial Stenosis (SAMMPRIS) trial has recently shown a robust impact of intensive medical therapy reducing the risk of clinical recurrence of symptomatic ICAS. However, even under best medical therapy and degree of risk factor control, symptomatic ICAS-related recurrence risk continues to be the highest among all stroke etiologic subtypes. The second part of the chapter reviews the current understanding of prognostic factors that may help discriminate the high-risk ICAS patients, divided into local factors (vulnerable ICAS plaque) and systemic factors (vulnerable ICAS patient). Regarding research on local factors, high-resolution magnetic resonance imaging (HRMRI) is an emerging technique that allows in vivo evaluation of intracranial arterial wall, which is displacing our research focus from intracranial stenosis degree towards intracranial atherosclerotic plaque composition and activity. Characterization of the vulnerable ICAS patient may be improved with biomarker research. The

  16. Prognostic factors in follicular lymphoma: new tools to personalize risk.

    Science.gov (United States)

    Casulo, Carla

    2016-12-02

    Follicular lymphoma (FL) is the most common indolent lymphoma, and it has a long median overall survival (OS). However, the recent discovery of clinical and biological prognostic biomarkers in FL is shedding light on FL heterogeneity and the need for a precise and risk-stratified individual approach at diagnosis and relapse. Many FL patients who are asymptomatic with indolent disease can be vulnerable to the toxicity, emotional distress, and financial burden of overtreatment. Yet a subset of FL patients develop chemoresistance to standard chemoimmunotherapy, experience transformation to aggressive lymphoma and rapid progression, and represent the population most in need of novel therapies and curative approaches. Novel biomarkers that incorporate both clinical and genetic determinants of poor risk are being developed with the hope of identifying high-risk patients at diagnosis in order to offer biologically rational targeted therapies. © 2016 by The American Society of Hematology. All rights reserved.

  17. Prognostic Importance of Circulating Tumor Cells in Nonsmall Cell ...

    African Journals Online (AJOL)

    Purpose: To investigate the prognostic value of circulating tumor cells (CTCs) and to predict the treatment response in a non-small cell lung cancer (NSCLC). Methodology: A single-center prospective study involving 93 patients with NSCLC was conducted. Blood samples were analyzed for CTC count before and after ...

  18. Cardiac biomarkers in Neonatology

    OpenAIRE

    Vijlbrief, D.C.

    2015-01-01

    In this thesis, the role for cardiac biomarkers in neonatology was investigated. Several clinically relevant results were reported. In term and preterm infants, hypoxia and subsequent adaptation play an important role in cardiac biomarker elevation. The elevated natriuretic peptides are indicative of abnormal function; elevated troponins are suggestive for cardiomyocyte damage. This methodology makes these biomarkers of additional value in the treatment of newborn infants, separate or as a co...

  19. A prognostic profile of hypoxia-induced genes for localised high-grade soft tissue sarcoma

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Sørensen, Brita Singers; Overgaard, Jens

    2016-01-01

    sarcoma (STS). METHODS: The hypoxia-induced gene quantification was performed by real-time quantitative PCR (RT-qPCR) of formalin-fixed, paraffin-embedded tissue samples. The gene expression cut-points were determined in a test cohort of 55 STS patients and used to allocate each patient into a more......BACKGROUND: For decades, tumour hypoxia has been pursued as a cancer treatment target. However, prognostic and predictive biomarkers are essential for the use of this target in the clinic. This study investigates the prognostic value of a hypoxia-induced gene profile in localised soft tissue...

  20. Towards Prognostics for Electronics Components

    Data.gov (United States)

    National Aeronautics and Space Administration — Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is...

  1. Modeling for Battery Prognostics

    Science.gov (United States)

    Kulkarni, Chetan S.; Goebel, Kai; Khasin, Michael; Hogge, Edward; Quach, Patrick

    2017-01-01

    For any battery-powered vehicles (be it unmanned aerial vehicles, small passenger aircraft, or assets in exoplanetary operations) to operate at maximum efficiency and reliability, it is critical to monitor battery health as well performance and to predict end of discharge (EOD) and end of useful life (EOL). To fulfil these needs, it is important to capture the battery's inherent characteristics as well as operational knowledge in the form of models that can be used by monitoring, diagnostic, and prognostic algorithms. Several battery modeling methodologies have been developed in last few years as the understanding of underlying electrochemical mechanics has been advancing. The models can generally be classified as empirical models, electrochemical engineering models, multi-physics models, and molecular/atomist. Empirical models are based on fitting certain functions to past experimental data, without making use of any physicochemical principles. Electrical circuit equivalent models are an example of such empirical models. Electrochemical engineering models are typically continuum models that include electrochemical kinetics and transport phenomena. Each model has its advantages and disadvantages. The former type of model has the advantage of being computationally efficient, but has limited accuracy and robustness, due to the approximations used in developed model, and as a result of such approximations, cannot represent aging well. The latter type of model has the advantage of being very accurate, but is often computationally inefficient, having to solve complex sets of partial differential equations, and thus not suited well for online prognostic applications. In addition both multi-physics and atomist models are computationally expensive hence are even less suited to online application An electrochemistry-based model of Li-ion batteries has been developed, that captures crucial electrochemical processes, captures effects of aging, is computationally efficient

  2. 18F-FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer's disease (AD) patients at the mild cognitive impairment (MCI) stage

    International Nuclear Information System (INIS)

    Morbelli, Silvia; Bauckneht, Matteo; Buschiazzo, Ambra; Nieri, Alberto; Sambuceti, Gianmario; Pagani, Marco; De Carli, Fabrizio

    2017-01-01

    We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer's disease (MCI-AD). We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F-fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal

  3. 18F-FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer's disease (AD) patients at the mild cognitive impairment (MCI) stage

    Energy Technology Data Exchange (ETDEWEB)

    Morbelli, Silvia; Bauckneht, Matteo; Buschiazzo, Ambra; Nieri, Alberto; Sambuceti, Gianmario [Genoa Univ. (Italy). Dept. of Health Sciences; IRCCS AOU San Martino-IST, Genoa (Italy). Nuclear Medicine Unit; Arnaldi, Dario; Picco, Agnese; Pardini, Matteo; Brugnolo, Andrea; Girtler, Nicola; Nobili, Flavio [Genoa Univ. (Italy). Clinical Neurology, Department of Neuroscience (DINOGMI); IRCCS AOU San Martino-IST, Genoa (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Stockholm (Sweden). Department of Nuclear Medicine; Chincarini, Andrea [Istituto Nazionale di Fisica Nucleare, Genoa (Italy); De Carli, Fabrizio [National Research Council, Genoa (Italy). Institute of Bioimaging and Molecular Physiology

    2017-11-15

    We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer's disease (MCI-AD). We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F-fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal

  4. Long-term results and prognostic factors in patients with stage III-IVA squamous cell carcinoma of the cervix treated with concurrent chemoradiotherapy from a single institution study

    International Nuclear Information System (INIS)

    Kudaka, Wataru; Nagai, Yutaka; Toita, Takafumi

    2013-01-01

    We evaluated the longer-term efficacy and safety of concurrent chemoradiotherapy (CCRT) incorporating high-dose-rate intracavitary brachytherapy (HDR-ICBT) with a lower cumulative radiotherapy (RT) protocol and analyzed prognostic risk factors for survival among patients with International Federation of Gynecology and Obstetrics (FIGO) stage III-IVA squamous cell carcinoma (SCC) of the cervix. Ninety-nine patients with FIGO stage III-IVA SCC of the cervix between 1997 and 2008 were treated with CCRT using cisplatin 20 mg/m 2 for 5 days every 3 weeks or 40 mg/m 2 weekly. Acute and late toxicities were evaluated. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method. The Cox proportional hazard model was used for multivariate analysis. Median age was 53.5 years. Median follow-up period was 58 months (range 6-170 months). Pathologically complete response was achieved in 93 patients (96.9%). The 5-year OS and DFS were 72.0 and 69.3%, respectively. The 5-year local and distant DFS were 83.0 and 75.1%, respectively. Thirty-one patients (31.3%) experienced recurrence. Multivariate analysis showed that tumor size and pretreatment hemoglobin level remained an independent risk factor for OS and DFS. Acute toxicity was moderate. In terms of late adverse effects, 2 patients (2.0%) suffered from grade 4 late intestinal toxicity because of radiation enterocolitis, with both requiring intestinal surgery. Our study demonstrates that the CCRT schedule in patients with FIGO stage III-IVA SCC is efficacious and safe. In addition, the assessment of tumor size and pretreatment anemia can provide valuable prognostic information. (author)

  5. Profiling biomarkers of traumatic axonal injury: From mouse to man.

    Science.gov (United States)

    Manivannan, Susruta; Makwana, Milan; Ahmed, Aminul Islam; Zaben, Malik

    2018-05-18

    Traumatic brain injury (TBI) poses a major public health problem on a global scale. Its burden results from high mortality and significant morbidity in survivors. This stems, in part, from an ongoing inadequacy in diagnostic and prognostic indicators despite significant technological advances. Traumatic axonal injury (TAI) is a key driver of the ongoing pathological process following TBI, causing chronic neurological deficits and disability. The science underpinning biomarkers of TAI has been a subject of many reviews in recent literature. However, in this review we provide a comprehensive account of biomarkers from animal models to clinical studies, bridging the gap between experimental science and clinical medicine. We have discussed pathogenesis, temporal kinetics, relationships to neuro-imaging, and, most importantly, clinical applicability in order to provide a holistic perspective of how this could improve TBI diagnosis and predict clinical outcome in a real-life setting. We conclude that early and reliable identification of axonal injury post-TBI with the help of body fluid biomarkers could enhance current care of TBI patients by (i) increasing speed and accuracy of diagnosis, (ii) providing invaluable prognostic information, (iii) allow efficient allocation of rehabilitation services, and (iv) provide potential therapeutic targets. The optimal model for assessing TAI is likely to involve multiple components, including several blood biomarkers and neuro-imaging modalities, at different time points. Copyright © 2018. Published by Elsevier B.V.

  6. Tumor antigens as proteogenomic biomarkers in invasive ductal carcinomas

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Campos, Benito; Winther, Ole

    2014-01-01

    directly linked to the hallmarks of cancer. The results found by proteogenomic analysis of the 32 tumor antigens studied here, capture largely the same pathway irregularities as those elucidated from large-scale screening of genomics analyses, where several thousands of genes are often found......Background: The majority of genetic biomarkers for human cancers are defined by statistical screening of high-throughput genomics data. While a large number of genetic biomarkers have been proposed for diagnostic and prognostic applications, only a small number have been applied in the clinic....... Similarly, the use of proteomics methods for the discovery of cancer biomarkers is increasing. The emerging field of proteogenomics seeks to enrich the value of genomics and proteomics approaches by studying the intersection of genomics and proteomics data. This task is challenging due to the complex nature...

  7. Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

    Directory of Open Access Journals (Sweden)

    Andrés Quesada

    Full Text Available This study analyzes the fluorimetric determination of alanyl- (Ala, glutamyl- (Glu, leucyl-cystinyl- (Cys and aspartyl-aminopeptidase (AspAp urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG, albumin, and neutrophil gelatinase-associated lipocalin (NGAL. Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259 with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

  8. Real-Time Prognostics of a Rotary Valve Actuator

    Science.gov (United States)

    Daigle, Matthew

    2015-01-01

    Valves are used in many domains and often have system-critical functions. As such, it is important to monitor the health of valves and their actuators and predict remaining useful life. In this work, we develop a model-based prognostics approach for a rotary valve actuator. Due to limited observability of the component with multiple failure modes, a lumped damage approach is proposed for estimation and prediction of damage progression. In order to support the goal of real-time prognostics, an approach to prediction is developed that does not require online simulation to compute remaining life, rather, a function mapping the damage state to remaining useful life is found offline so that predictions can be made quickly online with a single function evaluation. Simulation results demonstrate the overall methodology, validating the lumped damage approach and demonstrating real-time prognostics.

  9. Single nucleotide polymorphism rs13042395 in the SLC52A3 gene as a biomarker for regional lymph node metastasis and relapse-free survival of esophageal squamous cell carcinoma patients

    International Nuclear Information System (INIS)

    Tan, Hua-Zhen; Wu, Zhi-Yong; Wu, Jian-Yi; Long, Lin; Jiao, Ji-Wei; Peng, Yu-Hui; Xu, Yi-Wei; Li, Shan-Shan; Wang, Wei; Zhang, Jian-Jun; Li, En-Min; Xu, Li-Yan

    2016-01-01

    SLC52A3 was recently identified as a susceptibility gene for esophageal squamous cell carcinoma (ESCC). However, associations between the single nucleotide polymorphisms (SNPs) rs13042395 (C > T) and rs3746803 (G > A) in SLC52A3 and risk, tumor characteristics and survival of ESCC patients remain inconclusive and of unknown prognostic significance. Analyses of the association between SNPs in SLC52A3 and ESCC risk were performed on 479 ESCC cases, together with 479 controls, in a case-control study. Blood samples for cases and controls were collected and genotyped by real-time polymerase chain reaction (PCR) using TaqMan assays. Among the 479 ESCC cases, 343 cases with complete clinical data were used to investigate the association between SNPs and ESCC clinical characteristics; 288 cases with complete clinical data and 5-year follow-up data were used to analyze the association between SNPs and prognosis. Dual luciferase reporter assays and electrophoretic mobility shift assays (EMSAs) were used to investigate the biological function of rs13042395. No association was found between SLC52A3 rs3746803 and susceptibility, tumor characteristics or survival of ESCC patients. For rs13042395, TT genotype carriers were likely to have reduced lymph node metastasis (odds ratio (OR) = 0.55, 95 % confidence interval (CI), 0.31–0.98) and longer relapse-free survival time (P = 0.03) . Also, both rs13042395 (hazard ratio (HR) = 0.62, 95 % CI, 0.38–0.99) and regional lymph node metastasis (HR = 2.06, 95 % CI, 1.36–3.13 for N1 vs. N0; HR = 2.88, 95 % CI, 1.70–4.86 for N2 vs. N0; HR = 2.08, 95 % CI, 1.01–4.30 for N3 vs. N0) were independent factors affecting relapse-free survival for ESCC patients who underwent surgery. Dual luciferase reporter assays and EMSAs suggested that the CC genotype of rs13042395 enhanced SLC52A3 expression, probably via binding with specific transcription factors. The rs13042395 polymorphism in SLC52A3 is associated with regional lymph node

  10. Biomarkers in Autism

    Directory of Open Access Journals (Sweden)

    Robert eHendren

    2014-08-01

    Full Text Available Autism spectrum disorders (ASD are complex, heterogeneous disorders caused by an interaction between genetic vulnerability and environmental factors. In an effort to better target the underlying roots of ASD for diagnosis and treatment, efforts to identify reliable biomarkers in genetics, neuroimaging, gene expression and measures of the body’s metabolism are growing. For this article, we review the published studies of potential biomarkers in autism and conclude that while there is increasing promise of finding biomarkers that can help us target treatment, there are none with enough evidence to support routine clinical use unless medical illness is suspected. Promising biomarkers include those for mitochondrial function, oxidative stress, and immune function. Genetic clusters are also suggesting the potential for useful biomarkers.

  11. Prognostic features and markers for testicular cancer management

    Directory of Open Access Journals (Sweden)

    Eddy S Leman

    2010-01-01

    Full Text Available Testicular neoplasm accounts for about 1% of all cancers in men. Over the last 40 years, the incidence of testicular cancer has increased in northern European male populations for unknown reasons. When diagnosed at early stage, testicular cancer is usually curable with a high survival rate. In the past three decades, successful multidisciplinary approaches for the management of testicular cancer have significantly increased patient survival rates. Utilization of tumor markers and accurate prognostic classification has also contributed to successful therapy. In this article, we highlight the most commonly used tumor markers and several potential "novel" markers for testicular cancer as part of the ongoing effort in biomarker research and discovery. In addition, this article also identifies several key prognostic features that have been demonstrated to play a role in predicting relapse. These features include tumor size, rete testis invasion, lymphovascular invasion, and tumor histology. Together with tumor markers, these prognostic factors should be taken into account for risk-adapted management of testicular cancer.

  12. Biomarkers of Aging: From Function to Molecular Biology

    Directory of Open Access Journals (Sweden)

    Karl-Heinz Wagner

    2016-06-01

    Full Text Available Aging is a major risk factor for most chronic diseases and functional impairments. Within a homogeneous age sample there is a considerable variation in the extent of disease and functional impairment risk, revealing a need for valid biomarkers to aid in characterizing the complex aging processes. The identification of biomarkers is further complicated by the diversity of biological living situations, lifestyle activities and medical treatments. Thus, there has been no identification of a single biomarker or gold standard tool that can monitor successful or healthy aging. Within this short review the current knowledge of putative biomarkers is presented, focusing on their application to the major physiological mechanisms affected by the aging process including physical capability, nutritional status, body composition, endocrine and immune function. This review emphasizes molecular and DNA-based biomarkers, as well as recent advances in other biomarkers such as microRNAs, bilirubin or advanced glycation end products.

  13. Prognostic significance of miR-205 in endometrial cancer.

    Directory of Open Access Journals (Sweden)

    Mihriban Karaayvaz

    Full Text Available microRNAs have emerged as key regulators of gene expression, and their altered expression has been associated with tumorigenesis and tumor progression. Thus, microRNAs have potential as both cancer biomarkers and/or potential novel therapeutic targets. Although accumulating evidence suggests the role of aberrant microRNA expression in endometrial carcinogenesis, there are still limited data available about the prognostic significance of microRNAs in endometrial cancer. The goal of this study is to investigate the prognostic value of selected key microRNAs in endometrial cancer by the analysis of archival formalin-fixed paraffin-embedded tissues.Total RNAs were extracted from 48 paired normal and endometrial tumor specimens using Trizol based approach. The expression of miR-26a, let-7g, miR-21, miR-181b, miR-200c, miR-192, miR-215, miR-200c, and miR-205 were quantified by real time qRT-PCR expression analysis. Targets of the differentially expressed miRNAs were quantified using immunohistochemistry. Statistical analysis was performed by GraphPad Prism 5.0.The expression levels of miR-200c (P<0.0001 and miR-205 (P<0.0001 were significantly increased in endometrial tumors compared to normal tissues. Kaplan-Meier survival analysis revealed that high levels of miR-205 expression were associated with poor patient overall survival (hazard ratio, 0.377; Logrank test, P = 0.028. Furthermore, decreased expression of a miR-205 target PTEN was detected in endometrial cancer tissues compared to normal tissues.miR-205 holds a unique potential as a prognostic biomarker in endometrial cancer.

  14. Prognostic markers for colorectal cancer: estimating ploidy and stroma.

    Science.gov (United States)

    Danielsen, H E; Hveem, T S; Domingo, E; Pradhan, M; Kleppe, A; Syvertsen, R A; Kostolomov, I; Nesheim, J A; Askautrud, H A; Nesbakken, A; Lothe, R A; Svindland, A; Shepherd, N; Novelli, M; Johnstone, E; Tomlinson, I; Kerr, R; Kerr, D J

    2018-03-01

    We report here the prognostic value of ploidy and digital tumour-stromal morphometric analyses using material from 2624 patients with early stage colorectal cancer (CRC). DNA content (ploidy) and stroma-tumour fraction were estimated using automated digital imaging systems and DNA was extracted from sections of formalin-fixed paraffin-embedded (FFPE) tissue for analysis of microsatellite instability. Samples were available from 1092 patients recruited to the QUASAR 2 trial and two large observational series (Gloucester, n = 954; Oslo University Hospital, n = 578). Resultant biomarkers were analysed for prognostic impact using 5-year cancer-specific survival (CSS) as the clinical end point. Ploidy and stroma-tumour fraction were significantly prognostic in a multivariate model adjusted for age, adjuvant treatment, and pathological T-stage in stage II patients, and the combination of ploidy and stroma-tumour fraction was found to stratify these patients into three clinically useful groups; 5-year CSS 90% versus 83% versus 73% [hazard ratio (HR) = 1.77 (95% confidence interval (95% CI): 1.13-2.77) and HR = 2.95 (95% CI: 1.73-5.03), P < 0.001]. A novel biomarker, combining estimates of ploidy and stroma-tumour fraction, sampled from FFPE tissue, identifies stage II CRC patients with low, intermediate or high risk of CRC disease specific death, and can reliably stratify clinically relevant patient sub-populations with differential risks of tumour recurrence and may support choice of adjuvant therapy for these individuals.

  15. The use of mass spectrometry for analysing metabolite biomarkers in epidemiology

    DEFF Research Database (Denmark)

    Lind, Mads Vendelbo; Savolainen, Otto I; Ross, Alastair B

    2016-01-01

    measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many...... biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses...

  16. Procalcitonin Improves the Glasgow Prognostic Score for Outcome Prediction in Emergency Patients with Cancer: A Cohort Study

    Directory of Open Access Journals (Sweden)

    Anna Christina Rast

    2015-01-01

    Full Text Available The Glasgow Prognostic Score (GPS is useful for predicting long-term mortality in cancer patients. Our aim was to validate the GPS in ED patients with different cancer-related urgency and investigate whether biomarkers would improve its accuracy. We followed consecutive medical patients presenting with a cancer-related medical urgency to a tertiary care hospital in Switzerland. Upon admission, we measured procalcitonin (PCT, white blood cell count, urea, 25-hydroxyvitamin D, corrected calcium, C-reactive protein, and albumin and calculated the GPS. Of 341 included patients (median age 68 years, 61% males, 81 (23.8% died within 30 days after admission. The GPS showed moderate prognostic accuracy (AUC 0.67 for mortality. Among the different biomarkers, PCT provided the highest prognostic accuracy (odds ratio 1.6 (95% confidence interval 1.3 to 1.9, P<0.001, AUC 0.69 and significantly improved the GPS to a combined AUC of 0.74 (P=0.007. Considering all investigated biomarkers, the AUC increased to 0.76 (P<0.001. The GPS performance was significantly improved by the addition of PCT and other biomarkers for risk stratification in ED cancer patients. The benefit of early risk stratification by the GPS in combination with biomarkers from different pathways should be investigated in further interventional trials.

  17. YKL-40 protein expression is not a prognostic marker in patients with primary breast cancer

    DEFF Research Database (Denmark)

    Roslind, Anne; Knoop, Ann; Jensen, Maj-Britt

    2007-01-01

    in tumor tissue was assessed by immunohistochemistry in a cohort of 630 high-risk breast cancer patients with a median estimated potential follow-up time of 10 and 13 years for disease-free (DFS) and overall survival (OS), respectively. YKL-40 protein expression was found in malignant tumor cells......YKL-40 is a new biomarker in serum with a prognostic value in several localized and metastatic malignancies. The current knowledge regarding the biological functions of YKL-40 in cancer links YKL-40 to increased aggressiveness of the tumor. Utilizing tissue microarrays, YKL-40 protein expression...... and in inflammatory cells. High expression was associated with positive estrogen and progesterone receptor status and high tumor differentiation. Contrary to studies on serum YKL-40 as a prognostic biomarker, a high YKL-40 expression in tumor cells was not significantly associated with DSF and OS in univariate...

  18. New and emerging biomarkers in left ventricular systolic dysfunction--insight into dilated cardiomyopathy.

    Science.gov (United States)

    Gopal, Deepa M; Sam, Flora

    2013-08-01

    Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance, impaired contraction and dilation of the left ventricle (or both ventricles). Blood markers--known as "biomarkers"--allow insight into underlying pathophysiologic mechanisms and biologic pathways while predicting outcomes and guiding heart failure management and/or therapies. In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment, integrating these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones, and (h) renal biomarkers. Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure.

  19. Independent Prognostic Value of Stroke Volume Index in Patients With Immunoglobulin Light Chain Amyloidosis.

    Science.gov (United States)

    2018-05-01

    Heart involvement is the most important prognostic determinant in AL amyloidosis patients. Echocardiography is a cornerstone for the diagnosis and provides important prognostic information. We studied 754 patients with AL amyloidosis who underwent echocardiographic assessment at the Mayo Clinic, including a Doppler-derived measurement of stroke volume (SV) within 30 days of their diagnosis to explore the prognostic role of echocardiographic variables in the context of a well-established soluble cardiac biomarker staging system. Reproducibility of SV, myocardial contraction fraction, and left ventricular strain was assessed in a separate, yet comparable, study cohort of 150 patients from the Pavia Amyloidosis Center. The echocardiographic measures most predictive for overall survival were SV index <33 mL/min, myocardial contraction fraction <34%, and cardiac index <2.4 L/min/m 2 with respective hazard ratios (95% confidence intervals) of 2.95 (2.37-3.66), 2.36 (1.96-2.85), and 2.32 (1.91-2.80). For the subset that had left ventricular strain performed, the prognostic cut point was -14% (hazard ratios, 2.70; 95% confidence intervals, 1.84-3.96). Each parameter was independent of systolic blood pressure, Mayo staging system (NT-proBNP [N-terminal pro-B-type natriuretic peptide] and troponin), and ejection fraction on multivariable analysis. Simple predictive models for survival, including biomarker staging along with SV index or left ventricular strain, were generated. SV index prognostic performance was similar to left ventricular strain in predicting survival in AL amyloidosis, independently of biomarker staging. Because SV index is routinely calculated and widely available, it could serve as the preferred echocardiographic measure to predict outcomes in AL amyloidosis patients. © 2018 American Heart Association, Inc.

  20. Context-dependent interpretation of the prognostic value of BRAF and KRAS mutations in colorectal cancer

    International Nuclear Information System (INIS)

    Popovici, Vlad; Budinska, Eva; Bosman, Fred T; Tejpar, Sabine; Roth, Arnaud D; Delorenzi, Mauro

    2013-01-01

    The mutation status of the BRAF and KRAS genes has been proposed as prognostic biomarker in colorectal cancer. Of them, only the BRAF V600E mutation has been validated independently as prognostic for overall survival and survival after relapse, while the prognostic value of KRAS mutation is still unclear. We investigated the prognostic value of BRAF and KRAS mutations in various contexts defined by stratifications of the patient population. We retrospectively analyzed a cohort of patients with stage II and III colorectal cancer from the PETACC-3 clinical trial (N = 1,423), by assessing the prognostic value of the BRAF and KRAS mutations in subpopulations defined by all possible combinations of the following clinico-pathological variables: T stage, N stage, tumor site, tumor grade and microsatellite instability status. In each such subpopulation, the prognostic value was assessed by log rank test for three endpoints: overall survival, relapse-free survival, and survival after relapse. The significance level was set to 0.01 for Bonferroni-adjusted p-values, and a second threshold for a trend towards statistical significance was set at 0.05 for unadjusted p-values. The significance of the interactions was tested by Wald test, with significance level of 0.05. In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors, with higher effects than in the whole population. There was no evidence for prognostic value in microsatellite instable or right-sided tumor groups. We found that BRAF was also prognostic for relapse-free survival in some subpopulations. We found no evidence that KRAS mutations had prognostic value, although a trend was observed in some stratifications. We also show evidence of heterogeneity in survival of patients with BRAF V600E mutation. The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in

  1. Expression and prognostic value of EGR1 and EGR3 in gliomas

    DEFF Research Database (Denmark)

    Møldrup Knudsen, Arnon

    Introduction Gliomas are the most frequent primary brain tumors. For the most malignant glioma – the glioblastoma - the median survival is below 15 months. Since only few prognostic biomarkers are of benefit in daily practice, new markers are urgently needed. EGR1 and EGR3 are transcription factors...... involved in the regulation of cell-cycle, but they have also been associated with the migration of cancer cells. Studies have shown prognostic potential of EGR1 and EGR3 in breast-, gastric-, colorectal-, and prostate cancer. The purpose of this study was to investigate the expression and potential....... Cox proportional hazards regression showed that a high EGR1 fraction remained a significant prognostic variable when adjusted for confounders, both in all gliomas as one group (P=0.048) and glioblastomas exclusively (P=0.011). The combination of EGR1 high/EGR3 low in glioblastomas also remained...

  2. Prognostic value of long non-coding RNA MALAT1 in cancer patients.

    Science.gov (United States)

    Wu, Yihua; Lu, Wei; Xu, Jinming; Shi, Yu; Zhang, Honghe; Xia, Dajing

    2016-01-01

    Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) was identified to be the first long non-coding RNA as a biomarker of independent prognostic value for early stage non-small cell lung cancer patient survival. In recent years, the association between upregulated tissue MALAT1 level and incidence of various cancers including bladder cancer, colorectal cancer, and renal cancer has been widely discussed. The aim of our present study was to assess the potential prognostic value of MALAT1 in various human cancers. PubMed, Embase, Ovid, and Cochrane Library databases were systematically searched, and eligible studies evaluating the prognostic value of MALAT1 in various cancers were included. Finally, 11 studies encompassing 1216 participants reporting with sufficient data were enrolled in the current meta-analysis. The pooled hazard ratio (HR) was 2.05 (95 % confidence interval (CI) 1.64-2.55, p < 0.01) for overall survival (OS) and 2.66 (95 % CI 1.86-3.80, p < 0.01) for disease-free survival (DFS). In conclusion, high tissue MALAT1 level was associated with an inferior clinical outcome in various cancers, suggesting that MALAT1 might serve as a potential prognostic biomarker for various cancers.

  3. Histology-Based Expression Profiling Yields Novel Prognostic Markers in Human Glioblastoma

    Science.gov (United States)

    Dong, Shumin; Nutt, Catherine L.; Betensky, Rebecca A.; Stemmer-Rachamimov, Anat O.; Denko, Nicholas C.; Ligon, Keith L.; Rowitch, David H.; Louis, David N.

    2006-01-01

    Although the prognosis for patients with glioblastoma is poor, survival is variable, with some patients surviving longer than others. For this reason, there has been longstanding interest in the identi-fication of prognostic markers for glioblastoma. We hypothesized that specific histologic features known to correlate with malignancy most likely express molecules that are directly related to the aggressive behavior of these tumors. We further hypothesized that such molecules could be used as biomarkers to predict behavior in a manner that might add prognostic power to sole histologic observation of the feature. We reasoned that perinecrotic tumor cell palisading, which denotes the most aggressive forms of malignant gliomas, would be a striking histologic feature on which to test this hypothesis. We therefore used laser capture microdissection and oligonucleotide arrays to detect molecules differentially expressed in perinecrotic palisades. A set of RNAs (including POFUT2, PTDSR, PLOD2, ATF5, and HK2) that were differentially expressed in 3 initially studied, micro-dissected glioblastomas also provided prognostic information in an independent set of 28 glioblastomas that did not all have perinecrotic palisades. On validation in a second, larger independent series, this approach could be applied to other human glioma types to derive tissue biomarkers that could offer ancillary prognostic and predictive information alongside standard histopathologic examination. PMID:16254489

  4. Distributed Prognostics Based on Structural Model Decomposition

    Data.gov (United States)

    National Aeronautics and Space Administration — Within systems health management, prognostics focuses on predicting the remaining useful life of a system. In the model-based prognostics paradigm, physics-based...

  5. Biomarker Gene Signature Discovery Integrating Network Knowledge

    Directory of Open Access Journals (Sweden)

    Holger Fröhlich

    2012-02-01

    Full Text Available Discovery of prognostic and diagnostic biomarker gene signatures for diseases, such as cancer, is seen as a major step towards a better personalized medicine. During the last decade various methods, mainly coming from the machine learning or statistical domain, have been proposed for that purpose. However, one important obstacle for making gene signatures a standard tool in clinical diagnosis is the typical low reproducibility of these signatures combined with the difficulty to achieve a clear biological interpretation. For that purpose in the last years there has been a growing interest in approaches that try to integrate information from molecular interaction networks. Here we review the current state of research in this field by giving an overview about so-far proposed approaches.

  6. Biomarkers of postoperative delirium and cognitive dysfunction

    Directory of Open Access Journals (Sweden)

    Ganna eAndrosova

    2015-06-01

    Full Text Available Elderly surgical patients frequently experience postoperative delirium (POD and the subsequent development of postoperative cognitive dysfunction (POCD. Clinical features include deterioration in cognition, disturbance in attention and reduced awareness of the environment and result in higher morbidity, mortality and greater utilization of social financial assistance. The aging Western societies can expect an increase in the incidence of POD and POCD. The underlying pathophysiological mechanisms have been studied on the molecular level albeit with unsatisfying small research efforts given their societal burden. Here, we review the known physiological and immunological changes and genetic risk factors, identify candidates for further studies and integrate the information into a draft network for exploration on a systems level. The pathogenesis of these postoperative cognitive impairments is multifactorial; application of integrated systems biology has the potential to reconstruct the underlying network of molecular mechanisms and help in the identification of prognostic and diagnostic biomarkers.

  7. Biomarkers in Airway Diseases

    Directory of Open Access Journals (Sweden)

    Janice M Leung

    2013-01-01

    Full Text Available The inherent limitations of spirometry and clinical history have prompted clinicians and scientists to search for surrogate markers of airway diseases. Although few biomarkers have been widely accepted into the clinical armamentarium, the authors explore three sources of biomarkers that have shown promise as indicators of disease severity and treatment response. In asthma, exhaled nitric oxide measurements can predict steroid responsiveness and sputum eosinophil counts have been used to titrate anti-inflammatory therapies. In chronic obstructive pulmonary disease, inflammatory plasma biomarkers, such as fibrinogen, club cell secretory protein-16 and surfactant protein D, can denote greater severity and predict the risk of exacerbations. While the multitude of disease phenotypes in respiratory medicine make biomarker development especially challenging, these three may soon play key roles in the diagnosis and management of airway diseases.

  8. amphibian_biomarker_data

    Data.gov (United States)

    U.S. Environmental Protection Agency — Amphibian metabolite data used in Snyder, M.N., Henderson, W.M., Glinski, D.G., Purucker, S. T., 2017. Biomarker analysis of american toad (Anaxyrus americanus) and...

  9. Validation of New Cancer Biomarkers

    DEFF Research Database (Denmark)

    Duffy, Michael J; Sturgeon, Catherine M; Söletormos, Georg

    2015-01-01

    BACKGROUND: Biomarkers are playing increasingly important roles in the detection and management of patients with cancer. Despite an enormous number of publications on cancer biomarkers, few of these biomarkers are in widespread clinical use. CONTENT: In this review, we discuss the key steps...... in advancing a newly discovered cancer candidate biomarker from pilot studies to clinical application. Four main steps are necessary for a biomarker to reach the clinic: analytical validation of the biomarker assay, clinical validation of the biomarker test, demonstration of clinical value from performance...... of the biomarker test, and regulatory approval. In addition to these 4 steps, all biomarker studies should be reported in a detailed and transparent manner, using previously published checklists and guidelines. Finally, all biomarker studies relating to demonstration of clinical value should be registered before...

  10. Using Aptamers for Cancer Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    Yun Min Chang

    2013-01-01

    Full Text Available Aptamers are single-stranded synthetic DNA- or RNA-based oligonucleotides that fold into various shapes to bind to a specific target, which includes proteins, metals, and molecules. Aptamers have high affinity and high specificity that are comparable to that of antibodies. They are obtained using iterative method, called (Systematic Evolution of Ligands by Exponential Enrichment SELEX and cell-based SELEX (cell-SELEX. Aptamers can be paired with recent advances in nanotechnology, microarray, microfluidics, and other technologies for applications in clinical medicine. One particular area that aptamers can shed a light on is biomarker discovery. Biomarkers are important in diagnosis and treatment of cancer. In this paper, we will describe ways in which aptamers can be used to discover biomarkers for cancer diagnosis and therapeutics.

  11. Biomarkers in critical illness: have we made progress?

    Directory of Open Access Journals (Sweden)

    Honore PM

    2016-10-01

    Full Text Available Patrick M Honore,1 Rita Jacobs,1 Inne Hendrickx,1 Elisabeth De Waele,1 Viola Van Gorp,1 Olivier Joannes-Boyau,2 Jouke De Regt,1 Willem Boer,3 Herbert D Spapen1 1Intensive Care Unit, Universitair Ziekenhuis Brussel, VUB University, Brussels, Belgium; 2Intensive Care Unit, Hopital Haut Leveque, University of Bordeaux 2, Bordeaux, France; 3Intensive Care Unit, Ziekenhuis Oost-Limburg, Genk, Belgium Abstract: Biomarkers have emerged as exemplary key players in translational medicine. Many have been assessed for timely recognition, early treatment, and adequate follow-up for a variety of pathologies. Biomarker sensitivity has improved considerably over the last years but specificity remains poor, in particular when two “marker-sensitive” conditions overlap in one patient. Biomarker research holds an enormous potential for diagnostic and prognostic purposes in postoperative and critically ill patients who present varying degrees of inflammation, infection, and concomitant (subacute organ dysfunction or failure. Despite a remarkable progress in development and testing, biomarkers are not yet ready for routine use at the bedside. Keywords: biomarkers, acute kidney injury, sepsis, ARDS

  12. Clinical, functional, behavioural and epigenomic biomarkers of obesity.

    Science.gov (United States)

    Lafortuna, Claudio L; Tovar, Armando R; Rastelli, Fabio; Tabozzi, Sarah A; Caramenti, Martina; Orozco-Ruiz, Ximena; Aguilar-Lopez, Miriam; Guevara-Cruz, Martha; Avila-Nava, Azalia; Torres, Nimbe; Bertoli, Gloria

    2017-06-01

    Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects. Analysing these different biomarkers, we identified their potential role in diagnosis, prognosis and treatment. Epigenetic biomarkers, cellular mediators of inflammation and factors related to microbiota-host interactions may be considered to have a theranostic value. Though, the molecular processes responsible for the biological phenomenology detected by the other analysed markers, is not clear yet. Nevertheless, these biomarkers possess valuable diagnostic and prognostic power. A new frontier for theranostic biomarkers can be foreseen in the exploitation of parameters defining behaviours and lifestyles linked to the risk of obesity, capable to describe the effects of interventions for obesity prevention and treatment which include also behaviour change strategies.

  13. Amyotrophic lateral sclerosis multiprotein biomarkers in peripheral blood mononuclear cells.

    Directory of Open Access Journals (Sweden)

    Giovanni Nardo

    Full Text Available Amyotrophic lateral sclerosis (ALS is a fatal progressive motor neuron disease, for which there are still no diagnostic/prognostic test and therapy. Specific molecular biomarkers are urgently needed to facilitate clinical studies and speed up the development of effective treatments.We used a two-dimensional difference in gel electrophoresis approach to identify in easily accessible clinical samples, peripheral blood mononuclear cells (PBMC, a panel of protein biomarkers that are closely associated with ALS. Validations and a longitudinal study were performed by immunoassays on a selected number of proteins. The same proteins were also measured in PBMC and spinal cord of a G93A SOD1 transgenic rat model. We identified combinations of protein biomarkers that can distinguish, with high discriminatory power, ALS patients from healthy controls (98%, and from patients with neurological disorders that may resemble ALS (91%, between two levels of disease severity (90%, and a number of translational biomarkers, that link responses between human and animal model. We demonstrated that TDP-43, cyclophilin A and ERp57 associate with disease progression in a longitudinal study. Moreover, the protein profile changes detected in peripheral blood mononuclear cells of ALS patients are suggestive of possible intracellular pathogenic mechanisms such as endoplasmic reticulum stress, nitrative stress, disturbances in redox regulation and RNA processing.Our results indicate that PBMC multiprotein biomarkers could contribute to determine amyotrophic lateral sclerosis diagnosis, differential diagnosis, disease severity and progression, and may help to elucidate pathogenic mechanisms.

  14. Biomarkers in prostate cancer - Current clinical utility and future perspectives.

    Science.gov (United States)

    Kretschmer, Alexander; Tilki, Derya

    2017-12-01

    Current tendencies in the treatment course of prostate cancer patients increase the need for reliable biomarkers that help in decision-making in a challenging clinical setting. Within the last decade, several novel biomarkers have been introduced. In the following comprehensive review article, we focus on diagnostic (PHI ® , 4K score, SelectMDx ® , ConfirmMDx ® , PCA3, MiPS, ExoDX ® , mpMRI) and prognostic (OncotypeDX GPS ® , Prolaris ® , ProMark ® , DNA-ploidy, Decipher ® ) biomarkers that are in widespread clinical use and are supported by evidence. Hereby, we focus on multiple clinical situations in which innovative biomarkers may guide decision-making in prostate cancer therapy. In addition, we describe novel liquid biopsy approaches (circulating tumor cells, cell-free DNA) that have been described as predictive biomarkers in metastatic castration-resistant prostate cancer and might support an individual patient-centred oncological approach in the nearer future. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Follicular lymphoma international prognostic index

    NARCIS (Netherlands)

    Solal-Céligny, Philippe; Roy, Pascal; Colombat, Philippe; White, Josephine; Armitage, Jim O.; Arranz-Saez, Reyes; Au, Wing Y.; Bellei, Monica; Brice, Pauline; Caballero, Dolores; Coiffier, Bertrand; Conde-Garcia, Eulogio; Doyen, Chantal; Federico, Massimo; Fisher, Richard I.; Garcia-Conde, Javier F.; Guglielmi, Cesare; Hagenbeek, Anton; Haïoun, Corinne; LeBlanc, Michael; Lister, Andrew T.; Lopez-Guillermo, Armando; McLaughlin, Peter; Milpied, Noël; Morel, Pierre; Mounier, Nicolas; Proctor, Stephen J.; Rohatiner, Ama; Smith, Paul; Soubeyran, Pierre; Tilly, Hervé; Vitolo, Umberto; Zinzani, Pier-Luigi; Zucca, Emanuele; Montserrat, Emili

    2004-01-01

    The prognosis of follicular lymphomas (FL) is heterogeneous and numerous treatments may be proposed. A validated prognostic index (PI) would help in evaluating and choosing these treatments. Characteristics at diagnosis were collected from 4167 patients with FL diagnosed between 1985 and 1992.

  16. Prognostic stratification of ulcerated melanoma

    DEFF Research Database (Denmark)

    Bønnelykke-Behrndtz, Marie L; Schmidt, Henrik; Christensen, Ib J

    2014-01-01

    OBJECTIVES: For patients with melanoma, ulceration is an important prognostic marker and interestingly also a predictive marker for the response of adjuvant interferon. A consensual definition and accurate assessment of ulceration are therefore crucial for proper staging and clinical management. We...

  17. Baseline Cardiopulmonary Function as an Independent Prognostic Factor for Survival of Inoperable Non-Small-Cell Lung Cancer After Concurrent Chemoradiotherapy: A Single-Center Analysis of 161 Cases

    International Nuclear Information System (INIS)

    Semrau, Sabine; Klautke, Gunther; Fietkau, Rainer

    2011-01-01

    Purpose: Little is known about the effects of cardiopulmonary function on the prognosis of concurrent chemoradiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). Methods and Materials: A retrospective analysis of the effects of tumor- and patient-related factors and parameters of cardiopulmonary function and heart morphology on the feasibility, toxicity, and prognosis was performed. Results: Cardiopulmonary function had no effect on the toxicity or feasibility of treatment; effects on survival were observed in the univariate analysis. Median survival varied as follows: cardiac function: 13.0 ± 1.6 months for left ventricular ejection fraction (LVEF) > 50% vs. 10.0 ± 1.9 months for LVEF ≤ 50% (p = 0.003); pulmonary function: 16.0 ± 0.6 months for no lung function deficits (vital capacity [VC] ≥ 60%, forced expiratory volume in 1 s ≥ 80%, and diffusing capacity of the lung for carbon monoxide (DLCO) ≥60%) vs. 14.0 ± 1.5 months for one or two function deficits vs. 8.0 ± 1.5 months for three lung function deficits (p = 0.001); T stage: 19.0 ± 3.1 months for rcT0/cT1/cT2 vs. 12.0 ± 0.8 months for cT3/cT4 (p = 0.039); and age: 11.0 ± 1.5 months for <60 years vs. 18.0 ± 2.5 months for 60-69 years vs. 12.0 ± 1.2 months for ≥70 years (p = 0.008). Prognostic factors identified in the multivariate analysis were LVEF ≤50% (p = 0.043; hazard ratio [HR], 1.74), reduced pulmonary function (p = 0.001; HR, 1.71 or 5.05) and T stage (p = 0.026; HR: 1.71). Conclusions: In addition to T-stage, cardiac and pulmonary function variables affected the survival of non-small-cell lung cancer patients after chemoradiotherapy.

  18. Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

    Science.gov (United States)

    Hainfellner, J A; Heinzl, H

    2010-01-01

    Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

  19. Prognostic factors in childhood intracranial neoplasms

    International Nuclear Information System (INIS)

    Ampil, F.L.

    1987-01-01

    Thirty-six cases of primary intracranial neoplasm in children (over 1 year but under 13 years of age) seen at the university medical center between 1951 and 1982 were reviewed because of concern as to the results and after-effects of applied therapy. The overall 5-year actuarial survival rate was 17 %. Several factors of possible prognostic relevance, such as patient's age, intracranial location of the tumor, application or nonapplication of therapy, single or multiple modes of therapy, and extent of surgery, were analyzed. Completeness of surgical removal of the tumor proved to be the only statistically significant factor that correlated with survival. There was only one recorded case of severe learning disability and abnormal neuropsychologic development among the 12 living patients. The influence of patient's age (and technical factors) at the time of irradiation in correlation with the child's subsequent posttreatment functional performance, as reported in the literature, is reviewed. (author)

  20. Co-expression of periostin and EGFR in patients with esophageal squamous cell carcinoma and their prognostic significance

    Directory of Open Access Journals (Sweden)

    Jia W

    2016-08-01

    Full Text Available Wei Jia,1 Wei Wang,1 Chu-shu Ji,1 Jun-yang Niu,2 Ya-jing Lv,1 Hang-cheng Zhou,2 Bing Hu1 1Department of Medical Oncology, 2Department of Pathology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China Background: Both periostin (PN and epidermal growth factor receptor (EGFR can predict the prognosis of several carcinomas alone. However, coexpression of PN and EGFR in esophageal squamous cell carcinoma (ESCC still remains unknown. We aimed to clarify their relationship with clinicopathological factors and prognostic significance of their coexpression in ESCC. Patients and methods: In this single-center retrospective study, immunohistochemistry was performed to evaluate the expression of PN and EGFR in ESCC and paracarcinomatous tissues of 83 patients. The quantitative expression levels of PN and EGFR were examined in two ESCC and tumor-adjacent tissues. The levels of PN and EGFR expression were correlated with clinicopathological parameters by the χ2 or Kruskal–Wallis method. Spearman’s rank correlation test was performed to determine the relationship between PN and EGFR expression levels. Kaplan–Meier and Cox regression analyses were used to detect the prognostic factors of disease-free survival (DFS and overall survival (OS. Results: The high expression of PN protein in ESCC tissues was significantly associated with tumor length (P=0.044, differentiation grade (P=0.003, venous invasion (P=0.010, invasion depth (P=0.007, lymphatic metastasis (P=0.000, and tumor stage (P=0.000. The high expression of EGFR protein in ESCC tissues was only significantly related to lymphatic metastasis (P=0.000, invasion depth (P=0.022, and tumor stage (P=0.000. Kaplan–Meier analysis showed that high expression of PN was closely correlated to reduced OS (P=0.000 and DFS (P=0.000, which was consistent with EGFR expression. Cox regression analysis identified PN and EGFR as independent poor prognostic factors of OS and DFS

  1. Distributed Prognostics and Health Management with a Wireless Network Architecture

    Science.gov (United States)

    Goebel, Kai; Saha, Sankalita; Sha, Bhaskar

    2013-01-01

    A heterogeneous set of system components monitored by a varied suite of sensors and a particle-filtering (PF) framework, with the power and the flexibility to adapt to the different diagnostic and prognostic needs, has been developed. Both the diagnostic and prognostic tasks are formulated as a particle-filtering problem in order to explicitly represent and manage uncertainties in state estimation and remaining life estimation. Current state-of-the-art prognostic health management (PHM) systems are mostly centralized in nature, where all the processing is reliant on a single processor. This can lead to a loss in functionality in case of a crash of the central processor or monitor. Furthermore, with increases in the volume of sensor data as well as the complexity of algorithms, traditional centralized systems become for a number of reasons somewhat ungainly for successful deployment, and efficient distributed architectures can be more beneficial. The distributed health management architecture is comprised of a network of smart sensor devices. These devices monitor the health of various subsystems or modules. They perform diagnostics operations and trigger prognostics operations based on user-defined thresholds and rules. The sensor devices, called computing elements (CEs), consist of a sensor, or set of sensors, and a communication device (i.e., a wireless transceiver beside an embedded processing element). The CE runs in either a diagnostic or prognostic operating mode. The diagnostic mode is the default mode where a CE monitors a given subsystem or component through a low-weight diagnostic algorithm. If a CE detects a critical condition during monitoring, it raises a flag. Depending on availability of resources, a networked local cluster of CEs is formed that then carries out prognostics and fault mitigation by efficient distribution of the tasks. It should be noted that the CEs are expected not to suspend their previous tasks in the prognostic mode. When the

  2. Improved prediction of breast cancer outcome by identifying heterogeneous biomarkers.

    Science.gov (United States)

    Choi, Jonghwan; Park, Sanghyun; Yoon, Youngmi; Ahn, Jaegyoon

    2017-11-15

    Identification of genes that can be used to predict prognosis in patients with cancer is important in that it can lead to improved therapy, and can also promote our understanding of tumor progression on the molecular level. One of the common but fundamental problems that render identification of prognostic genes and prediction of cancer outcomes difficult is the heterogeneity of patient samples. To reduce the effect of sample heterogeneity, we clustered data samples using K-means algorithm and applied modified PageRank to functional interaction (FI) networks weighted using gene expression values of samples in each cluster. Hub genes among resulting prioritized genes were selected as biomarkers to predict the prognosis of samples. This process outperformed traditional feature selection methods as well as several network-based prognostic gene selection methods when applied to Random Forest. We were able to find many cluster-specific prognostic genes for each dataset. Functional study showed that distinct biological processes were enriched in each cluster, which seems to reflect different aspect of tumor progression or oncogenesis among distinct patient groups. Taken together, these results provide support for the hypothesis that our approach can effectively identify heterogeneous prognostic genes, and these are complementary to each other, improving prediction accuracy. https://github.com/mathcom/CPR. jgahn@inu.ac.kr. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  3. Prognostic factors in Hodgkin's disease stage III with special reference to tumour burden

    DEFF Research Database (Denmark)

    Specht, L; Nissen, N I

    1988-01-01

    143 patients with Hodgkin's disease stage III (65 PS III, 78 CS III) were treated with radiotherapy alone (33 patients), combination chemotherapy alone (56 patients), or radiotherapy plus combination chemotherapy (54 patients). They were followed till death or from 7 to 191 months. Prognostic fac...... regarding early stage disease to the effect that tumour burden is the single most important prognostic factor in Hodgkin's disease....

  4. MicroRNAs in prostate cancer: Functional role as biomarkers.

    Science.gov (United States)

    Kanwal, Rajnee; Plaga, Alexis R; Liu, Xiaoqi; Shukla, Girish C; Gupta, Sanjay

    2017-10-28

    MicroRNAs (miRNAs) are small endogenous non-coding molecules that alters gene expression through post-transcriptional regulation of messenger RNA. Compelling evidence suggest the role of miRNA in cancer biology having potential as diagnostic, prognostic and predictive biomarkers. This review summarizes the current knowledge on miRNA deregulated in prostate cancer and their role as oncogene, tumor suppressor and metastasis regulators. The emerging information elucidating the biological function of miRNA is promising and may lead to their potential usefulness as diagnostic/prognostic markers and development as effective therapeutic tools for management of prostate cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Biomarkers of sepsis

    Science.gov (United States)

    2013-01-01

    Sepsis is an unusual systemic reaction to what is sometimes an otherwise ordinary infection, and it probably represents a pattern of response by the immune system to injury. A hyper-inflammatory response is followed by an immunosuppressive phase during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infection. Biomarkers to diagnose sepsis may allow early intervention which, although primarily supportive, can reduce the risk of death. Although lactate is currently the most commonly used biomarker to identify sepsis, other biomarkers may help to enhance lactate’s effectiveness; these include markers of the hyper-inflammatory phase of sepsis, such as pro-inflammatory cytokines and chemokines; proteins such as C-reactive protein and procalcitonin which are synthesized in response to infection and inflammation; and markers of neutrophil and monocyte activation. Recently, markers of the immunosuppressive phase of sepsis, such as anti-inflammatory cytokines, and alterations of the cell surface markers of monocytes and lymphocytes have been examined. Combinations of pro- and anti-inflammatory biomarkers in a multi-marker panel may help identify patients who are developing severe sepsis before organ dysfunction has advanced too far. Combined with innovative approaches to treatment that target the immunosuppressive phase, these biomarkers may help to reduce the mortality rate associated with severe sepsis which, despite advances in supportive measures, remains high. PMID:23480440

  6. Novel biomarkers for prediabetes, diabetes, and associated complications

    Science.gov (United States)

    Dorcely, Brenda; Katz, Karin; Jagannathan, Ram; Chiang, Stephanie S; Oluwadare, Babajide; Goldberg, Ira J; Bergman, Michael

    2017-01-01

    The number of individuals with prediabetes is expected to grow substantially and estimated to globally affect 482 million people by 2040. Therefore, effective methods for diagnosing prediabetes will be required to reduce the risk of progressing to diabetes and its complications. The current biomarkers, glycated hemoglobin (HbA1c), fructosamine, and glycated albumin have limitations including moderate sensitivity and specificity and are inaccurate in certain clinical conditions. Therefore, identification of additional biomarkers is being explored recognizing that any single biomarker will also likely have inherent limitations. Therefore, combining several biomarkers may more precisely identify those at high risk for developing prediabetes and subsequent progression to diabetes. This review describes recently identified biomarkers and their potential utility for addressing the burgeoning epidemic of dysglycemic disorders. PMID:28860833

  7. Mass spectrometry for biomarker development

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Chaochao; Liu, Tao; Baker, Erin Shammel; Rodland, Karin D.; Smith, Richard D.

    2015-06-19

    Biomarkers potentially play a crucial role in early disease diagnosis, prognosis and targeted therapy. In the past decade, mass spectrometry based proteomics has become increasingly important in biomarker development due to large advances in technology and associated methods. This chapter mainly focuses on the application of broad (e.g. shotgun) proteomics in biomarker discovery and the utility of targeted proteomics in biomarker verification and validation. A range of mass spectrometry methodologies are discussed emphasizing their efficacy in the different stages in biomarker development, with a particular emphasis on blood biomarker development.

  8. Novel biomarkers for risk stratification in pulmonary arterial hypertension

    Directory of Open Access Journals (Sweden)

    Thomas Zelniker

    2015-10-01

    Full Text Available Risk stratification in pulmonary arterial hypertension (PAH is paramount to identifying individuals at highest risk of death. So far, there are only limited parameters for prognostication in patients with PAH. 95 patients with confirmed PAH were included in the present analysis and followed for a total of 4 years. Blood samples were analysed for serum levels of N-terminal pro-brain natriuretic peptide, high-sensitivity troponin T (hsTnT, pro-atrial natriuretic peptide (proANP, growth differentiation factor 15, soluble fms-like tyrosine kinase 1 and placental growth factor. 27 (28.4% patients died during a follow-up of 4 years. Levels of all tested biomarkers, except for placental growth factor, were significantly elevated in nonsurvivors compared with survivors. Receiver operating characteristic analyses demonstrated that cardiac biomarkers had the highest power in predicting mortality. In particular, proANP exhibited the highest area under the curve, followed by N-terminal pro-brain natriuretic peptide and hsTnT. Furthermore, proANP and hsTnT added significant additive prognostic value to the established markers in categorical and continuous net reclassification index. Moreover, after Cox regression, proANP (hazard ratio (HR 1.91, hsTnT (HR 1.41, echocardiographic right ventricular impairment (HR 1.30 and 6-min walk test (HR 0.97 per 10 m remained the only significant parameters in prognostication of mortality. Our data suggest benefits of the implementation of proANP and hsTnT as additive biomarkers for risk stratification in patients with PAH.

  9. Biomarkers of the Dementia

    Directory of Open Access Journals (Sweden)

    Mikio Shoji

    2011-01-01

    Full Text Available Recent advances in biomarker studies on dementia are summarized here. CSF Aβ40, Aβ42, total tau, and phosphorylated tau are the most sensitive biomarkers for diagnosis of Alzheimer's disease (AD and prediction of onset of AD from mild cognitive impairment (MCI. Based on this progress, new diagnostic criteria for AD, MCI, and preclinical AD were proposed by National Institute of Aging (NIA and Alzheimer's Association in August 2010. In these new criteria, progress in biomarker identification and amyloid imaging studies in the past 10 years have added critical information. Huge contributions of basic and clinical studies have established clinical evidence supporting these markers. Based on this progress, essential therapy for cure of AD is urgently expected.

  10. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    and previous cancer diagnoses compared to patients who were not diagnosed with cancer. Previous cancer, C-reactive protein (CRP) and suPAR were significantly associated with newly diagnosed cancer during follow-up in multiple logistic regression analyses adjusted for age, sex and CRP. Neither any of the PRRs......In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...

  11. Towards Prognostics for Electronics Components

    Science.gov (United States)

    Saha, Bhaskar; Celaya, Jose R.; Wysocki, Philip F.; Goebel, Kai F.

    2013-01-01

    Electronics components have an increasingly critical role in avionics systems and in the development of future aircraft systems. Prognostics of such components is becoming a very important research field as a result of the need to provide aircraft systems with system level health management information. This paper focuses on a prognostics application for electronics components within avionics systems, and in particular its application to an Isolated Gate Bipolar Transistor (IGBT). This application utilizes the remaining useful life prediction, accomplished by employing the particle filter framework, leveraging data from accelerated aging tests on IGBTs. These tests induced thermal-electrical overstresses by applying thermal cycling to the IGBT devices. In-situ state monitoring, including measurements of steady-state voltages and currents, electrical transients, and thermal transients are recorded and used as potential precursors of failure.

  12. Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Abildgaard, Mette Opstrup; Haldrup, Christa

    2013-01-01

    Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays...... in three hypermethylated prostate cell lines, suggesting epigenetic silencing. Negative APN immunoreactivity was significantly associated with short RFS and short CSS in the RP and CT cohort, respectively, independently of routine clinicopathological predictors. Combining APN with a known angiogenesis...... representing 267 radical prostatectomy (RP) and 111 conservatively treated (CT) PC patients. Clinical end points were recurrence-free survival (RFS) and cancer-specific survival (CSS), respectively. The ANPEP promoter methylation levels were determined by bisulphite sequencing or MethyLight analysis in 278...

  13. Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers.

    LENUS (Irish Health Repository)

    Jansen, Michael

    2010-07-01

    Over the past 10 years, there has been an increasing use of molecular markers in the assessment and management of adult malignant gliomas. Some molecular signatures are used diagnostically to help pathologists classify tumours, whereas others are used to estimate prognosis for patients. Most crucial, however, are those markers that are used to predict response to certain therapies, thereby directing clinicians to a particular treatment while avoiding other potentially deleterious therapies. Recently, large-scale genome-wide surveys have been used to identify new biomarkers that have been rapidly developed as diagnostic and prognostic tools. Given these developments, the pace of discovery of new molecular assays will quicken to facilitate personalised medicine in the setting of malignant glioma.

  14. Biomarker in Cisplatin-Based Chemotherapy for Urinary Bladder Cancer.

    Science.gov (United States)

    Ecke, Thorsten H

    2015-01-01

    The treatment of metastasized bladder cancer has been evolving during recent years. Cisplatin based chemotherapy combinations are still gold standard in the treatment of advanced and metastasized bladder cancer. But new therapies are approaching. Based to this fact biological markers will become more important for decisions in bladder cancer treatment. A systematic MEDLINE search of the key words "cisplatin", "bladder cancer", "DNA marker", "protein marker", "methylation biomarker", "predictive marker", "prognostic marker" has been made. This review aims to highlight the most relevant clinical and experimental studies investigating markers for metastasized transitional carcinoma of the urothelium treated by cisplatin based regimens.

  15. Prognostic factors in Acanthamoeba keratitis.

    Science.gov (United States)

    Kaiserman, Igor; Bahar, Irit; McAllum, Penny; Srinivasan, Sathish; Elbaz, Uri; Slomovic, Allan R; Rootman, David S

    2012-06-01

    To assess the prognostic factors influencing visual prognosis and length of treatment after acanthamoeba keratitis (AK). Forty-two AK eyes of 41 patients treated between 1999 and 2006 were included. A diagnosis of AK was made on the basis of culture results with a corresponding clinical presentation. We calculated the prognostic effect of the various factors on final visual acuity and the length of treatment. Multivariate regression analysis was used to adjust for the simultaneous effects of the various prognostic factors. Mean follow-up was 19.7 ± 21.0 months. Sixty-four percent of cases had > 1 identified risk factor for AK, the most common risk factor being contact lens wear (92.9% of eyes). At presentation, median best spectacle corrected visual acuity (BCVA) was 20/200 (20/30 to Hand Motion [HM]) that improved after treatment to 20/50 (20/20 to Counting Fingers [CF]). Infection acquired by swimming or related to contact lenses had significantly better final BCVA (p = 0.03 and p = 0.007, respectively). Neuritis and pseudodendrites were also associated with better final BCVA (p = 0.04 and p = 0.05, respectively). Having had an epithelial defect on presentation and having been treated with topical steroid were associated with worse final best spectacle corrected visual acuity (BSCVA) (p = 0.0006 and p = 0.04). Multivariate regression analysis found a good initial visual acuity (p = 0.002), infections related to swimming (p = 0.01), the absence of an epithelial defect (p = 0.03), having been treated with chlorhexidine (p = 0.05), and not having receive steroids (p = 0.003) to significantly forecast a good final BCVA. We identified several prognostic factors that can help clinicians evaluate the expected visual damage of the AK infection and thus tailor treatment accordingly. Copyright © 2012 Canadian Ophthalmological Society. All rights reserved.

  16. New and Emerging Biomarkers in Left Ventricular Systolic Dysfunction - Insight into Dilated Cardiomyopathy

    Science.gov (United States)

    Gopal, Deepa M.; Sam, Flora

    2013-01-01

    Background Dilated cardiomyopathy (DCM) is characterized by deteriorating cardiac performance and impaired contraction and dilation of the left (or both) ventricles. Blood markers – known as “biomarkers” allow insight into underlying pathophysiologic mechanisms and biologic pathways, while predicting outcomes and guiding heart failure management and/or therapies. Content In this review, we provide an alternative approach to conceptualize heart failure biomarkers: the cardiomyocyte, its surrounding microenvironment, and the macroenvironment with clear interaction between these entities which may impact cellular processes involved in the pathogenesis and/or propagation of DCM. Newer biomarkers of left ventricular systolic dysfunction can be categorized under: (a) myocyte stress and stretch, (b) myocyte apoptosis, (c) cardiac interstitium, (d) inflammation, (e) oxidative stress, (f) cardiac energetics, (g) neurohormones and (h) renal biomarkers. Summary Biomarkers provide insight into the pathogenesis of DCM while predicting and potentially providing prognostic information in these patients with heart failure. PMID:23609585

  17. Molecular Biomarkers in the Clinical Management of Prostate Cancer.

    Science.gov (United States)

    Udager, Aaron M; Tomlins, Scott A

    2018-01-08

    Prostate cancer, one of the most common noncutaneous malignancies in men, is a heterogeneous disease with variable clinical outcome. Although the majority of patients harbor indolent tumors that are essentially cured by local therapy, subsets of patients present with aggressive disease or recur/progress after primary treatment. With this in mind, modern clinical approaches to prostate cancer emphasize the need to reduce overdiagnosis and overtreatment via personalized medicine. Advances in our understanding of prostate cancer pathogenesis, coupled with recent technologic innovations, have facilitated the development and validation of numerous molecular biomarkers, representing a range of macromolecules assayed from a variety of patient sample types, to help guide the clinical management of prostate cancer, including early detection, diagnosis, prognostication, and targeted therapeutic selection. Herein, we review the current state of the art regarding prostate cancer molecular biomarkers, emphasizing those with demonstrated utility in clinical practice. Copyright © 2018 Cold Spring Harbor Laboratory Press; all rights reserved.

  18. Role of proteomics in the discovery of autism biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Ayadhi, L. A.; Halepoto, D. M. [King Saud Univ., Riyadh (Saudi Arabia). Dept. of Physiology

    2013-02-15

    The epidemiology of autism is continuously increasing all over the world with social, behavioural and economical burdens. Autism is considered as a multi-factorial disorder, influenced by genetic, neurological, environmental and immunological aspects. Autism is still believed to be incurable disorder with little information about the role of proteins patterns in the diagnosis of the disease. Knowing the applications of proteomic tools, it is possible to identify quantitative and qualitative protein patterns in a wide variety of tissues and body fluids such as blood, urine, saliva and cerebrospinal fluid in order to establish specific diagnostic and prognostic biomarkers. The aim of this review is to provide an overview of the various protocols available for proteomics by using mass spectrometry analysis, discuss reports in which these techniques have been previously applied in biomarker discovery for the diagnosis of autism, and consider the future development of this area of research. (author)

  19. Role of proteomics in the discovery of autism biomarkers

    International Nuclear Information System (INIS)

    Ayadhi, L.A.; Halepoto, D.M.

    2013-01-01

    The epidemiology of autism is continuously increasing all over the world with social, behavioural and economical burdens. Autism is considered as a multi-factorial disorder, influenced by genetic, neurological, environmental and immunological aspects. Autism is still believed to be incurable disorder with little information about the role of proteins patterns in the diagnosis of the disease. Knowing the applications of proteomic tools, it is possible to identify quantitative and qualitative protein patterns in a wide variety of tissues and body fluids such as blood, urine, saliva and cerebrospinal fluid in order to establish specific diagnostic and prognostic biomarkers. The aim of this review is to provide an overview of the various protocols available for proteomics by using mass spectrometry analysis, discuss reports in which these techniques have been previously applied in biomarker discovery for the diagnosis of autism, and consider the future development of this area of research. (author)

  20. Nasopharyngeal Carcinoma Signaling Pathway: An Update on Molecular Biomarkers

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    Warut Tulalamba

    2012-01-01

    Full Text Available Nasopharyngeal carcinoma (NPC is an uncommon cancer, which has a distinctive ethnic and geographic distribution. Etiology of NPC is considered to be related with a complex interaction of environmental and genetic factors as well as Epstein-Barr virus infection. Since NPC is located in the silent painless area, the disease is usually therefore diagnosed at the advanced stages; hence early detection of NPC is difficult. Furthermore, understanding in molecular pathogenesis is still lacking, pondering the identification of effective prognostic and diagnostic biomarkers. Dysregulation of signaling molecules in intracellular signal transduction, which regulate cell proliferation, apoptosis, and adhesion, underlines the basis of NPC pathogenesis. In this paper, the molecular signaling pathways in the NPC are discussed for the holistic view of NPC development and progression. The important insights toward NPC pathogenesis may offer strategies for identification of novel biomarkers for diagnosis and prognosis.

  1. PET imaging biomarkers in head and neck cancer

    Energy Technology Data Exchange (ETDEWEB)

    Differding, Sarah; Gregoire, Vincent [Universite Catholique de Louvain, St-Luc University Hospital, Department of Radiation Oncology, and Center for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Experimentale et Clinique (IREC), Brussels (Belgium); Hanin, Francois-Xavier [Universite Catholique de Louvain, St-Luc University Hospital, Department of Nuclear Medicine, and Center for Molecular Imaging, Radiotherapy and Oncology (MIRO), Institut de Recherche Experimentale et Clinique (IREC), Brussels (Belgium)

    2015-04-01

    In locally advanced head and neck squamous cell carcinoma (HNSCC), the role of imaging becomes more and more critical in the management process. In this framework, molecular imaging techniques such as PET allow noninvasive assessment of a range of tumour biomarkers such as metabolism, hypoxia and proliferation, which can serve different purposes. First, in a pretreatment setting they can influence therapy selection strategies and target delineation for radiation therapy. Second, their predictive and/or prognostic value could help enhance the therapeutic ratio in the management of HNSCC. Third, treatment modification can be performed through the generation of a molecular-based heterogeneous dose distribution with dose escalation to the most resistant parts of the tumour, a concept known as dose painting. Fourth, they are increasingly becoming a tool for monitoring response to therapy. In this review, PET imaging biomarkers used in the routine management of HNSCC or under investigation are discussed. (orig.)

  2. Circulating miRNAs as biomarkers for endocrine disorders.

    Science.gov (United States)

    Butz, H; Kinga, N; Racz, K; Patocs, A

    2016-01-01

    Specific, sensitive and non-invasive biomarkers are always needed in endocrine disorders. miRNAs are short, non-coding RNA molecules with well-known role in gene expression regulation. They are frequently dysregulated in metabolic and endocrine diseases. Recently it has been shown that they are secreted into biofluids by nearly all kind of cell types. As they can be taken up by other cells they may have a role in a new kind of paracrine, cell-to-cell communication. Circulating miRNAs are protected by RNA-binding proteins or microvesicles hence they can be attractive candidates as diagnostic or prognostic biomarkers. In this review, we summarize the characteristics of extracellular miRNA's and our knowledge about their origin and potential roles in endocrine and metabolic diseases. Discussions about the technical challenges occurring during identification and measurement of extracellular miRNAs and future perspectives about their roles are also highlighted.

  3. PROGNOSTICAL COMPETENCE OF THE FUTURE TEACHERS-ACTORS: TO THE ISSUE OF THE CONCEPT DEFINITION

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    Elena Viktorovna Tsalko

    2016-02-01

    Full Text Available In this paper on the basis of the notions of competence, forecasting, prognostical competence the author’s definition of future actors-teachers’ prognostical competence is developed. Under prognostic competence of future actors-teachers we understand a special competence that allows the subject, engaged in professional activities as a performer of roles in the theater (movies, TV, as well as performing teaching activities in the field of arts, to receive the necessary anticipatory information about the phenomenon under investigation (on performing roles in the theatre, films, and television, on the learning process and actors-teachers training. Components of prognostical competence as a type of competencies (cognitive, instrumental and operational and motivational-value are singled out. The feature of the future actor-teacher’s professional activities in the context of prognostical competence is viewed. It is the simultaneous solving the artistic-creative, organizational and teaching-upbringing problems.Purpose. The purpose of the paper is the definition of prognostical competence of future teachers-actors.Methodology. In the research the methods of theoretical level are used: comparison, analysis and synthesis, generalization, concretization; analytical methods; idealization and modeling.Result. The result of the research is the development of the author’s concept of «prognostical competence of the future teachers-actors».Practical implications. Application of the results: The results may be applied to the work of teachers-actors’ trainers as well as the researchers in Pedagogy.

  4. Prognostic significance of genetic polymorphisms in disease progression and survival in prostate cancer after androgen deprivation therapy

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    Tsung-Yi Huang

    2015-06-01

    Full Text Available It is believed that androgens and their receptors regulate normal prostate growth and mediate prostate cancer development. Androgen deprivation therapy is the most commonly used treatment for advanced prostate cancer. Although the therapy is initially effective, progression of the disease to castration-resistant prostate cancer is almost inevitable, leading to treatment failure. Despite the existence of current clinical parameters, new biomarkers are urgently needed to improve the prognosis. Some molecules and DNA-based genetic biomarkers are under investigation as potential prognostic factors. The advancement in molecular cytogenetic research, such as genome-wide association for single-nucleotide polymorphisms, has made possible the detection of genetic mutations. In this study, a literature search from August 1985 to April 2013 was performed through the PubMed database using the keywords “genetic polymorphisms”, “prostate cancer” and “androgen deprivation therapy”. The results revealed that several genome-wide association studies (such as rs16901979, rs7931342, HSD17B4, rs6162 in the CYP17A1, rs4243229 and rs7201637 in the HSD17B2, rs1062577 in the ESR1, SLCO1B3, SLCO2B1, rs2939244 in the ARRDC3, rs9508016 in the FLT1, rs6504145 in the SKAP1, rs7830611 in the FBXO32, rs9508016 in the FLT1, rs12529 in the AKR1C3, rs16934641 in the BNC2, rs3763763 in the TACC2, rs2051778 in the ALPK1, and rs3763763 in the TACC2, AR, ESR1, and ESR2 and single-nucleotide polymorphisms in important pathways (such as androgen signal, biosynthesis, metabolism, androgen receptor binding site, response element, androgen receptor CAG repeat polymorphism length, and estrogen receptor-binding sites involved in prostate cancer occurrence and mechanism could serve as candidate biomarkers for the early detection of castration-resistant prostate cancer after androgen deprivation therapy. Additional investigations are required to decipher precisely the gene

  5. Validation of α-Synuclein as a CSF Biomarker for Sporadic Creutzfeldt-Jakob Disease.

    Science.gov (United States)

    Llorens, Franc; Kruse, Niels; Karch, André; Schmitz, Matthias; Zafar, Saima; Gotzmann, Nadine; Sun, Ting; Köchy, Silja; Knipper, Tobias; Cramm, Maria; Golanska, Ewa; Sikorska, Beata; Liberski, Pawel P; Sánchez-Valle, Raquel; Fischer, Andre; Mollenhauer, Brit; Zerr, Inga

    2018-03-01

    The analysis of cerebrospinal fluid (CSF) biomarkers gains importance in the differential diagnosis of prion diseases. However, no single diagnostic tool or combination of them can unequivocally confirm prion disease diagnosis. Electrochemiluminescence (ECL)-based immunoassays have demonstrated to achieve high diagnostic accuracy in a variety of sample types due to their high sensitivity and dynamic range. Quantification of CSF α-synuclein (a-syn) by an in-house ECL-based ELISA assay has been recently reported as an excellent approach for the diagnosis of sporadic Creutzfeldt-Jakob disease (sCJD), the most prevalent form of human prion disease. In the present study, we validated a commercially available ECL-based a-syn ELISA platform as a diagnostic test for correct classification of sCJD cases. CSF a-syn was analysed in 203 sCJD cases with definite diagnosis and in 445 non-CJD cases. We investigated reproducibility and stability of CSF a-syn and made recommendations for its analysis in the sCJD diagnostic workup. A sensitivity of 98% and a specificity of 97% were achieved when using an optimal cut-off of 820 pg/mL a-syn. Moreover, we were able to show a negative correlation between a-syn levels and disease duration suggesting that CSF a-syn may be a good prognostic marker for sCJD patients. The present study validates the use of a-syn as a CSF biomarker of sCJD and establishes the clinical and pre-analytical parameters for its use in differential diagnosis in clinical routine. Additionally, the current test presents some advantages compared to other diagnostic approaches: it is fast, economic, requires minimal amount of CSF and a-syn levels are stable along disease progression.

  6. Prognostic implication of NQO1 overexpression in hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Lijuan; Sun, Jie; Tan, Yan; Li, Zhenling; Kong, Fanyong; Shen, Yue; Liu, Chao; Chen, Litian

    2017-11-01

    To explore the role of NQO1 overexpression for prognostic implication in hepatocellular carcinoma (HCC), NQO1 mRNA levels were detected in HCC fresh tissue samples of HCC and nontumor tissues, respectively. One hundred fifty-six cases of HCC meeting strict follow-up criteria were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological features of HCC were evaluated using χ 2 tests, survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient 5-year survival was analyzed using Cox proportional hazards analysis. In results, the levels of NQO1 mRNA were significantly up-regulated in 14 fresh tissue samples of HCC. Immunohistochemical analysis showed that the NQO1 expression and overexpression rates were significantly higher in HCC samples compared with either adjacent nontumor tissues or normal liver tissues. NQO1 overexpression correlated to tumor size, venous infiltration and late pTNM stage of HCC. NQO1 overexpression was also related to low disease-free survival and 5-year survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with NQO1 overexpression were significantly lower than those of patients without NQO1 expression. Further analysis using a Cox proportional hazards regression model revealed that NQO1 expression emerged as a significant independent hazard factor for the 5-year survival rate of patients with HCC. Therefore, NQO1 plays an important role in the progression of HCC. NQO1 may potentially be used as an independent biomarker for prognostic evaluation of HCC. Copyright © 2017. Published by Elsevier Inc.

  7. A novel prognostic six-CpG signature in glioblastomas.

    Science.gov (United States)

    Yin, An-An; Lu, Nan; Etcheverry, Amandine; Aubry, Marc; Barnholtz-Sloan, Jill; Zhang, Lu-Hua; Mosser, Jean; Zhang, Wei; Zhang, Xiang; Liu, Yu-He; He, Ya-Long

    2018-03-01

    We aimed to identify a clinically useful biomarker using DNA methylation-based information to optimize individual treatment of patients with glioblastoma (GBM). A six-CpG panel was identified by incorporating genome-wide DNA methylation data and clinical information of three distinct discovery sets and was combined using a risk-score model. Different validation sets of GBMs and lower-grade gliomas and different statistical methods were implemented for prognostic evaluation. An integrative analysis of multidimensional TCGA data was performed to molecularly characterize different risk tumors. The six-CpG risk-score signature robustly predicted overall survival (OS) in all discovery and validation cohorts and in a treatment-independent manner. It also predicted progression-free survival (PFS) in available patients. The multimarker epigenetic signature was demonstrated as an independent prognosticator and had better performance than known molecular indicators such as glioma-CpG island methylator phenotype (G-CIMP) and proneural subtype. The defined risk subgroups were molecularly distinct; high-risk tumors were biologically more aggressive with concordant activation of proangiogenic signaling at multimolecular levels. Accordingly, we observed better OS benefits of bevacizumab-contained therapy to high-risk patients in independent sets, supporting its implication in guiding usage of antiangiogenic therapy. Finally, the six-CpG signature refined the risk classification based on G-CIMP and MGMT methylation status. The novel six-CpG signature is a robust and independent prognostic indicator for GBMs and is of promising value to improve personalized management. © 2018 John Wiley & Sons Ltd.

  8. A CONCISE PANEL OF BIOMARKERS IDENTIFIES NEUROCOGNITIVE FUNCTIONING CHANGES IN HIV-INFECTED INDIVIDUALS

    Science.gov (United States)

    Marcotte, Thomas D.; Deutsch, Reena; Michael, Benedict Daniel; Franklin, Donald; Cookson, Debra Rosario; Bharti, Ajay R.; Grant, Igor; Letendre, Scott L.

    2013-01-01

    Background Neurocognitive (NC) impairment (NCI) occurs commonly in people living with HIV. Despite substantial effort, no biomarkers have been sufficiently validated for diagnosis and prognosis of NCI in the clinic. The goal of this project was to identify diagnostic or prognostic biomarkers for NCI in a comprehensively characterized HIV cohort. Methods Multidisciplinary case review selected 98 HIV-infected individuals and categorized them into four NC groups using normative data: stably normal (SN), stably impaired (SI), worsening (Wo), or improving (Im). All subjects underwent comprehensive NC testing, phlebotomy, and lumbar puncture at two timepoints separated by a median of 6.2 months. Eight biomarkers were measured in CSF and blood by immunoassay. Results were analyzed using mixed model linear regression and staged recursive partitioning. Results At the first visit, subjects were mostly middle-aged (median 45) white (58%) men (84%) who had AIDS (70%). Of the 73% who took antiretroviral therapy (ART), 54% had HIV RNA levels below 50 c/mL in plasma. Mixed model linear regression identified that only MCP-1 in CSF was associated with neurocognitive change group. Recursive partitioning models aimed at diagnosis (i.e., correctly classifying neurocognitive status at the first visit) were complex and required most biomarkers to achieve misclassification limits. In contrast, prognostic models were more efficient. A combination of three biomarkers (sCD14, MCP-1, SDF-1α) correctly classified 82% of Wo and SN subjects, including 88% of SN subjects. A combination of two biomarkers (MCP-1, TNF-α) correctly classified 81% of Im and SI subjects, including 100% of SI subjects. Conclusions This analysis of well-characterized individuals identified concise panels of biomarkers associated with NC change. Across all analyses, the two most frequently identified biomarkers were sCD14 and MCP-1, indicators of monocyte/macrophage activation. While the panels differed depending on

  9. Biomarkers for anorexia nervosa

    DEFF Research Database (Denmark)

    Sjøgren, Jan Magnus

    2017-01-01

    Biomarkers for anorexia nervosa (AN) which reflect the pathophysiology and relate to the aetiology of the disease, are warranted and could bring us one step closer to targeted treatment of AN. Some leads may be found in the biochemistry which often is found disturbed in AN, although normalization...

  10. Generic Software Architecture for Prognostics (GSAP) User Guide

    Science.gov (United States)

    Teubert, Christopher Allen; Daigle, Matthew John; Watkins, Jason; Sankararaman, Shankar; Goebel, Kai

    2016-01-01

    The Generic Software Architecture for Prognostics (GSAP) is a framework for applying prognostics. It makes applying prognostics easier by implementing many of the common elements across prognostic applications. The standard interface enables reuse of prognostic algorithms and models across systems using the GSAP framework.

  11. Exosomal miRNAs as biomarkers for prostate cancer

    Directory of Open Access Journals (Sweden)

    Nina Pettersen Hessvik

    2013-03-01

    Full Text Available miRNAs are small non-coding RNAs that finely regulate gene expression in cells. Alterations in miRNA expression have been associated with development of cancer, and miRNAs are now being investigated as biomarkers for cancer as well as other diseases. Recently, miRNAs have been found outside cells in body fluids. Extracellular miRNAs exist in different forms - associated with Ago2 proteins, loaded into extracellular vesicles (exosomes, microvesicles or apoptotic bodies or into high density lipoprotein particles. These extracellular miRNAs are probably products of distinct cellular processes, and might therefore play different roles. However, their functions in vivo are currently unknown. In spite of this, they are considered as promising, noninvasive diagnostic and prognostic tools. Prostate cancer is the most common cancer in men in the Western world, but the currently used biomarker (prostate specific antigen has low specificity. Therefore, novel biomarkers are highly needed. In this review we will discuss possible biological functions of extracellular miRNAs, as well as the potential use of miRNAs from extracellular vesicles as biomarkers for prostate cancer.

  12. Biomarkers of the extracellular matrix and of collagen fragments.

    Science.gov (United States)

    Chalikias, Georgios K; Tziakas, Dimitrios N

    2015-03-30

    A great body of evidence has shown that extracellular matrix (ECM) alterations are present in the major types of cardiac diseases: ischemic heart disease, heart disease associated with pressure overload, heart disease associated with volume overload, and intrinsic myocardial disease or cardiomyopathy. Collagen, type I and III, is the principal structural protein found in the myocardium and its pro- or telopeptides are released into the circulation during the course of cardiovascular diseases. Therefore, these peptides may reflect collagen synthesis and break-down and also represent a much more useful tool to address ECM changes from a distance. Clinical trials have been performed during recent years to examine the usage of these peptides as diagnostic or prognostic biomarkers in heart failure (HF) patients. This review aims to summarize published data concerning cardiac ECM and its circulating biomarkers. Studies that focused on collagen metabolism related biomarkers in patients with HF are analyzed. Finally, limitations associated with the clinical use of the aforementioned biomarkers are also discussed. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Biomarkers of cancer cachexia.

    Science.gov (United States)

    Loumaye, Audrey; Thissen, Jean-Paul

    2017-12-01

    Cachexia is a complex multifactorial syndrome, characterized by loss of skeletal muscle and fat mass, which affects the majority of advanced cancer patients and is associated with poor prognosis. Interestingly, reversing muscle loss in animal models of cancer cachexia leads to prolong survival. Therefore, detecting cachexia and maintaining muscle mass represent a major goal in the care of cancer patients. However, early diagnosis of cancer cachexia is currently limited for several reasons. Indeed, cachexia development is variable according to tumor and host characteristics. In addition, safe, accessible and non-invasive tools to detect skeletal muscle atrophy are desperately lacking in clinical practice. Finally, the precise molecular mechanisms and the key players involved in cancer cachexia remain poorly characterized. The need for an early diagnosis of cancer cachexia supports therefore the quest for a biomarker that might reflect skeletal muscle atrophy process. Current research offers different promising ways to identify such a biomarker. Initially, the quest for a biomarker of cancer cachexia has mostly focused on mediators of muscle atrophy, produced by both tumor and host, in an attempt to define new therapeutic approaches. In another hand, molecules released by the muscle into the circulation during the atrophy process have been also considered as potential biomarkers. More recently, several "omics" studies are emerging to identify new muscular or circulating markers of cancer cachexia. Some genetic markers could also contribute to identify patients more susceptible to develop cachexia. This article reviews our current knowledge regarding potential biomarkers of cancer cachexia. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  14. Prognostic value of baseline seric Syndecan-1 in initially unresectable metastatic colorectal cancer patients: a simple biological score.

    Science.gov (United States)

    Jary, Marine; Lecomte, Thierry; Bouché, Olivier; Kim, Stefano; Dobi, Erion; Queiroz, Lise; Ghiringhelli, Francois; Etienne, Hélène; Léger, Julie; Godet, Yann; Balland, Jérémy; Lakkis, Zaher; Adotevi, Olivier; Bonnetain, Franck; Borg, Christophe; Vernerey, Dewi

    2016-11-15

    In first-line metastatic colorectal cancer (mCRC), baseline prognostic factors allowing death risk and treatment strategy stratification are lacking. Syndecan-1 (CD138) soluble form was never described as a prognostic biomarker in mCRC. We investigated its additional prognostic value for overall survival (OS). mCRC patients with unresectable disease at diagnosis were treated with bevacizumab-based chemotherapy in two independent prospective clinical trials (development set: n = 126, validation set: n = 51, study NCT00489697 and study NCT00544011, respectively). Serums were collected at baseline for CD138 measurement. OS determinants were assessed and, based on the final multivariate model, a prognostic score was proposed. Two independent OS prognostic factors were identified: Lactate Dehydrogenase (LDH) high level (p = 0.0066) and log-CD138 high level (p = 0.0190). The determination of CD138 binary information (cutoff: 75 ng/mL) allowed the assessment of a biological prognostic score with CD138 and LDH values, identifying three risk groups for death (median OS= 38.9, 30.1 and 19.8 months for the low, intermediate and high risk groups, respectively; p value for OS, in mCRC patients. A simple biological scoring system is proposed including LDH and CD138 binary status values. © 2016 UICC.

  15. GERD—Barrett—Adenocarcinoma: Do We Have Suitable Prognostic and Predictive Molecular Markers?

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    Romana Illig

    2013-01-01

    Full Text Available Due to unfavorable lifestyle habits (unhealthy diet and tobacco abuse the incidence of gastroesophageal reflux disease (GERD in western countries is increasing. The GERD-Barrett-Adenocarcinoma sequence currently lacks well-defined diagnostic, progressive, predictive, and prognostic biomarkers (i providing an appropriate screening method identifying the presence of the disease, (ii estimating the risk of evolving cancer, that is, the progression from Barrett’s esophagus (BE to esophageal adenocarcinoma (EAC, (iii predicting the response to therapy, and (iv indicating an overall survival—prognosis for EAC patients. Based on histomorphological findings, detailed screening and therapeutic guidelines have been elaborated, although epidemiological studies could not support the postulated increasing progression rates of GERD to BE and EAC. Additionally, proposed predictive and prognostic markers are rather heterogeneous by nature, lack substantial proofs, and currently do not allow stratification of GERD patients for progression, outcome, and therapeutic effectiveness in clinical practice. The aim of this paper is to discuss the current knowledge regarding the GERD-BE-EAC sequence mainly focusing on the disputable and ambiguous status of proposed biomarkers to identify promising and reliable markers in order to provide more detailed insights into pathophysiological mechanisms and thus to improve prognostic and predictive therapeutic approaches.

  16. A Survey of Artificial Intelligence for Prognostics

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    National Aeronautics and Space Administration — Integrated Systems Health Management includes as key elements fault detection, fault diagnostics, and failure prognostics. Whereas fault detection and diagnostics...

  17. Metrics for Evaluating Performance of Prognostic Techniques

    Data.gov (United States)

    National Aeronautics and Space Administration — Prognostics is an emerging concept in condition basedmaintenance(CBM)ofcriticalsystems.Alongwith developing the fundamentals of being able to confidently predict...

  18. Simulating Degradation Data for Prognostic Algorithm Development

    Data.gov (United States)

    National Aeronautics and Space Administration — PHM08 Challenge Dataset is now publicly available at the NASA Prognostics Respository + Download INTRODUCTION - WHY SIMULATE DEGRADATION DATA? Of various challenges...

  19. A DISTRIBUTED PROGNOSTIC HEALTH MANAGEMENT ARCHITECTURE

    Data.gov (United States)

    National Aeronautics and Space Administration — This paper introduces a generic distributed prognostic health management (PHM) architecture with specific application to the electrical power systems domain. Current...

  20. Serum C-reactive protein (CRP) as a simple and independent prognostic factor in extranodal natural killer/T-cell lymphoma, nasal type.

    Science.gov (United States)

    Li, Ya-Jun; Li, Zhi-Ming; Xia, Yi; Huang, Jia-Jia; Huang, Hui-Qiang; Xia, Zhong-Jun; Lin, Tong-Yu; Li, Su; Cai, Xiu-Yu; Wu-Xiao, Zhi-Jun; Jiang, Wen-Qi

    2013-01-01

    C-reactive protein (CRP) is a biomarker of the inflammatory response, and it shows significant prognostic value for several types of solid tumors. The prognostic significance of CRP for lymphoma has not been fully examined. We evaluated the prognostic role of baseline serum CRP levels in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL). We retrospectively analyzed 185 patients with newly diagnosed ENKTL. The prognostic value of the serum CRP level was evaluated for the low-CRP group (CRP≤10 mg/L) versus the high-CRP group (CRP>10 mg/L). The prognostic value of the International Prognostic Index (IPI) and the Korean Prognostic Index (KPI) were evaluated and compared with the newly developed prognostic model. Patients in the high-CRP group tended to display increased adverse clinical characteristics, lower rates of complete remission (P60 years, hypoalbuminemia, and elevated lactate dehydrogenase levels were independent adverse predictors of OS. Based on these four independent predictors, we constructed a new prognostic model that identified 4 groups with varying OS: group 1, no adverse factors; group 2, 1 factor; group 3, 2 factors; and group 4, 3 or 4 factors (PKPI in distinguishing between the low- and intermediate-low-risk groups, the intermediate-low- and high-intermediate-risk groups, and the high-intermediate- and high-risk groups. Our results suggest that pretreatment serum CRP levels represent an independent predictor of clinical outcome for patients with ENKTL. The prognostic value of the new prognostic model is superior to both IPI and KPI.

  1. Array-based gene expression, CGH and tissue data defines a 12q24 gain in neuroblastic tumors with prognostic implication

    Directory of Open Access Journals (Sweden)

    Kilpinen Sami

    2010-05-01

    Full Text Available Abstract Background Neuroblastoma has successfully served as a model system for the identification of neuroectoderm-derived oncogenes. However, in spite of various efforts, only a few clinically useful prognostic markers have been found. Here, we present a framework, which integrates DNA, RNA and tissue data to identify and prioritize genetic events that represent clinically relevant new therapeutic targets and prognostic biomarkers for neuroblastoma. Methods A single-gene resolution aCGH profiling was integrated with microarray-based gene expression profiling data to distinguish genetic copy number alterations that were strongly associated with transcriptional changes in two neuroblastoma cell lines. FISH analysis using a hotspot tumor tissue microarray of 37 paraffin-embedded neuroblastoma samples and in silico data mining for gene expression information obtained from previously published studies including up to 445 healthy nervous system samples and 123 neuroblastoma samples were used to evaluate the clinical significance and transcriptional consequences of the detected alterations and to identify subsequently activated gene(s. Results In addition to the anticipated high-level amplification and subsequent overexpression of MYCN, MEIS1, CDK4 and MDM2 oncogenes, the aCGH analysis revealed numerous other genetic alterations, including microamplifications at 2p and 12q24.11. Most interestingly, we identified and investigated the clinical relevance of a previously poorly characterized amplicon at 12q24.31. FISH analysis showed low-level gain of 12q24.31 in 14 of 33 (42% neuroblastomas. Patients with the low-level gain had an intermediate prognosis in comparison to patients with MYCN amplification (poor prognosis and to those with no MYCN amplification or 12q24.31 gain (good prognosis (P = 0.001. Using the in silico data mining approach, we identified elevated expression of five genes located at the 12q24.31 amplicon in neuroblastoma (DIABLO, ZCCHC

  2. Blood Biomarkers in Idiopathic Pulmonary Fibrosis.

    Science.gov (United States)

    Guiot, Julien; Moermans, Catherine; Henket, Monique; Corhay, Jean-Louis; Louis, Renaud

    2017-06-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease of unknown origin whose incidence has been increasing over the latest decade partly as a consequence of population ageing. New anti-fibrotic therapy including pirfenidone and nintedanib have now proven efficacy in slowing down the disease. Nevertheless, diagnosis and follow-up of IPF remain challenging. This review examines the recent literature on potentially useful blood molecular and cellular biomarkers in IPF. Most of the proposed biomarkers belong to chemokines (IL-8, CCL18), proteases (MMP-1 and MMP-7), and growth factors (IGBPs) families. Circulating T cells and fibrocytes have also gained recent interest in that respect. Up to now, though several interesting candidates are profiling there has not been a single biomarker, which proved to be specific of the disease and predictive of the evolution (decline of pulmonary function test values, risk of acute exacerbation or mortality). Large scale multicentric studies are eagerly needed to confirm the utility of these biomarkers.

  3. Biomarkers of drug-induced vascular injury

    International Nuclear Information System (INIS)

    Brott, D.; Gould, S.; Jones, H.; Schofield, J.; Prior, H.; Valentin, J.P; Bjurstrom, S.; Kenne, K.; Schuppe-Koistinen, I.; Katein, A.; Foster-Brown, L.; Betton, G.; Richardson, R.; Evans, G.; Louden, C.

    2005-01-01

    In pre-clinical safety studies, drug-induced vascular injury is an issue of concern because there are no obvious diagnostic markers for pre-clinical or clinical monitoring and there is an intellectual gap in our understanding of the pathogenesis of this lesion. While vasodilatation and increased shear stress appear to play a role, the exact mechanism(s) of injury to the primary targets, smooth muscle and endothelial cells are unknown. However, evaluation of novel markers for potential clinical monitoring with a mechanistic underpinning would add value in risk assessment and management. This mini review focuses on the progress to identify diagnostic markers of drug-induced vascular injury. Von Willebrand factor (vWF), released upon perturbation of endothelial cells, is transiently increased in plasma prior to morphological evidence of damage in dogs or rats treated with vascular toxicants. Therefore, vWF might be a predictive biomarker of vascular injury. However, vWF is not an appropriate biomarker of lesion progression or severity since levels return to baseline values when there is morphological evidence of injury. A potential mechanistically linked biomarker of vascular injury is caveolin-1. Expression of this protein, localized primarily to smooth muscle and endothelial cells, decreases with the onset of vascular damage. Since vascular injury involves multiple mediators and cell types, evaluation of a panel rather than a single biomarker may be more useful in monitoring early and severe progressive vascular injury

  4. Prognostic value of age, subglottic, and anterior commissure involvement for early glottic carcinoma treated with CO2 laser transoral microsurgery: a retrospective, single-center cohort study of 261 patients.

    Science.gov (United States)

    Carta, Filippo; Bandino, Fabrizio; Olla, Aurora Marta; Chuchueva, Natalia; Gerosa, Clara; Puxeddu, Roberto

    2018-05-01

     CO 2 laser transoral microsurgery for glottic carcinoma, when indicated, has the well-established advantages of low morbidity and positive oncological outcomes. The present study aims to determine how patient age, and tumor site could negatively impact prognosis; other variables such as the status of the margins of resection, tobacco and alcohol intake, and the grade of differentiation of the tumors have been evaluated. This was a retrospective analysis on 261 patients with a glottic carcinoma who underwent CO 2 laser transoral microsurgery. The impact of different variables was calculated using univariate and multivariate analyses. The study included 248 males and 13 females. The median follow-up period was 4.3 years. Five-year disease-specific survival, recurrence-free survival, local control with laser alone, overall laryngeal preservation, and overall survival rates were 99.4, 92.2, 93.8, 97.6, and 85.5%, respectively. Equivalent results were observed in young and elderly patients. Patients with positive margins after CO 2 laser transoral microsurgery showed a reduced local control with laser alone. T2 patients with true subglottic spreading and patients with anterior commissure involvement of grade 3 (Rucci's classification) experienced worse local control rates, despite free surgical margins confirmed by histology.  CO 2 laser transoral microsurgery is an effective and reproducible single-stage modality therapy for young and elderly patients with glottic carcinoma. Superficial close margins can be managed by a careful wait-and-see policy, while positive margins should undergo surgical enlargement. In our experience, undifferentiated tumors, true subglottic extension, and anterior commissure involvement of grade 3 were associated with worse outcomes.

  5. Clinical variables serve as prognostic factors in a model for survival from glioblastoma multiforme: an observational study of a cohort of consecutive non-selected patients from a single institution

    International Nuclear Information System (INIS)

    Michaelsen, Signe Regner; Christensen, Ib Jarle; Grunnet, Kirsten; Stockhausen, Marie-Thérése; Broholm, Helle; Kosteljanetz, Michael; Poulsen, Hans Skovgaard

    2013-01-01

    Although implementation of temozolomide (TMZ) as a part of primary therapy for glioblastoma multiforme (GBM) has resulted in improved patient survival, the disease is still incurable. Previous studies have correlated various parameters to survival, although no single parameter has yet been identified. More studies and new approaches to identify the best and worst performing patients are therefore in great demand. This study examined 225 consecutive, non-selected GBM patients with performance status (PS) 0–2 receiving postoperative radiotherapy with concomitant and adjuvant TMZ as primary therapy. At relapse, patients with PS 0–2 were mostly treated by reoperation and/or combination with bevacizumab/irinotecan (BEV/IRI), while a few received TMZ therapy if the recurrence-free period was >6 months. Median overall survival and time to progression were 14.3 and 8.0 months, respectively. Second-line therapy indicated that reoperation and/or BEV/IRI increased patient survival compared with untreated patients and that BEV/IRI was more effective than reoperation alone. Patient age, ECOG PS, and use of corticosteroid therapy were significantly correlated with patient survival and disease progression on univariate analysis, whereas p53, epidermal growth factor receptor, and O 6 -methylguanine-DNA methyltransferase expression (all detected by immunohistochemistry), tumor size or multifocality, and extent of primary operation were not. A model based on age, ECOG PS, and corticosteroids use was able to predict survival probability for an individual patient. The survival of RT/TMZ-treated GBM patients can be predicted based on patient age, ECOG PS, and corticosteroid therapy status

  6. Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study.

    Science.gov (United States)

    Espelund, Ulrick; Renehan, Andrew G; Cold, Søren; Oxvig, Claus; Lancashire, Lee; Su, Zhenqiang; Flyvbjerg, Allan; Frystyk, Jan

    2018-05-03

    Measurement of circulating insulin-like growth factors (IGFs), in particular IGF-binding protein (IGFBP)-2, at the time of diagnosis, is independently prognostic in many cancers, but its clinical performance against other routinely determined prognosticators has not been examined. We measured IGF-I, IGF-II, pro-IGF-II, IGF bioactivity, IGFBP-2, -3, and pregnancy-associated plasma protein A (PAPP-A), an IGFBP regulator, in baseline samples of 301 women with breast cancer treated on four protocols (Odense, Denmark: 1993-1998). We evaluated performance characteristics (expressed as area under the curve, AUC) using Cox regression models to derive hazard ratios (HR) with 95% confidence intervals (CIs) for 10-year recurrence-free survival (RFS) and overall survival (OS), and compared those against the clinically used Nottingham Prognostic Index (NPI). We measured the same biomarkers in 531 noncancer individuals to assess multidimensional relationships (MDR), and evaluated additional prognostic models using survival artificial neural network (SANN) and survival support vector machines (SSVM), as these enhance capture of MDRs. For RFS, increasing concentrations of circulating IGFBP-2 and PAPP-A were independently prognostic [HR biomarker doubling : 1.474 (95% CIs: 1.160, 1.875, P = 0.002) and 1.952 (95% CIs: 1.364, 2.792, P < 0.001), respectively]. The AUC RFS for NPI was 0.626 (Cox model), improving to 0.694 (P = 0.012) with the addition of IGFBP-2 plus PAPP-A. Derived AUC RFS using SANN and SSVM did not perform superiorly. Similar patterns were observed for OS. These findings illustrate an important principle in biomarker qualification-measured circulating biomarkers may demonstrate independent prognostication, but this does not necessarily translate into substantial improvement in clinical performance. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  7. Biomarkers for personalized oncology: recent advances and future challenges.

    Science.gov (United States)

    Kalia, Madhu

    2015-03-01

    Cancer is a group of diseases characterized by the uncontrolled growth and spread of abnormal cells and oncology is a branch of medicine that deals with tumors. The last decade has seen significant advances in the development of biomarkers in oncology that play a critical role in understanding molecular and cellular mechanisms which drive tumor initiation, maintenance and progression. Clinical molecular diagnostics and biomarker discoveries in oncology are advancing rapidly as we begin to understand the complex mechanisms that transform a normal cell into an abnormal one. These discoveries have fueled the development of novel drug targets and new treatment strategies. The standard of care for patients with advanced-stage cancers has shifted away from an empirical treatment strategy based on the clinical-pathological profile to one where a biomarker driven treatment algorithm based on the molecular profile of the tumor is used. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation sequencing make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive (diagnostic) biomarkers are helpful in matching targeted therapies with patients and in preventing toxicity of standard (systemic) therapies. Prognostic biomarkers identify somatic germ line mutations, changes in DNA methylation, elevated levels of microRNA (miRNA) and circulating tumor cells (CTC) in blood. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of personalized oncotherapy for the treatment of five diseases: chronic myeloid leukemia, colon, breast, lung cancer and melanoma and these biomarkers are being used successfully to evaluate benefits that can be achieved through targeted therapy. Examples of these molecularly targeted biomarker therapies are: tyrosine kinase inhibitors in chronic myeloid leukemia and

  8. Biomarkers of Pediatric Brain Tumors

    Directory of Open Access Journals (Sweden)

    Mark D Russell

    2013-03-01

    Full Text Available Background and Need for Novel Biomarkers: Brain tumors are the leading cause of death by solid tumors in children. Although improvements have been made in their radiological detection and treatment, our capacity to promptly diagnose pediatric brain tumors in their early stages remains limited. This contrasts several other cancers where serum biomarkers such as CA 19-9 and CA 125 facilitate early diagnosis and treatment. Aim: The aim of this article is to review the latest literature and highlight biomarkers which may be of clinical use in the common types of primary pediatric brain tumor. Methods: A PubMed search was performed to identify studies reporting biomarkers in the bodily fluids of pediatric patients with brain tumors. Details regarding the sample type (serum, cerebrospinal fluid or urine, biomarkers analyzed, methodology, tumor type and statistical significance were recorded. Results: A total of 12 manuscripts reporting 19 biomarkers in 367 patients vs. 397 controls were identified in the literature. Of the 19 biomarkers identified, 12 were isolated from cerebrospinal fluid, 2 from serum, 3 from urine, and 2 from multiple bodily fluids. All but one study reported statistically significant differences in biomarker expression between patient and control groups.Conclusions: This review identifies a panel of novel biomarkers for pediatric brain tumors. It provides a platform for the further studies necessary to validate these biomarkers and, in addition, highlights several techniques through which new biomarkers can be discovered.

  9. [Prognostic scores for pulmonary embolism].

    Science.gov (United States)

    Junod, Alain

    2016-03-23

    Nine prognostic scores for pulmonary embolism (PE), based on retrospective and prospective studies, published between 2000 and 2014, have been analyzed and compared. Most of them aim at identifying PE cases with a low risk to validate their ambulatory care. Important differences in the considered outcomes: global mortality, PE-specific mortality, other complications, sizes of low risk groups, exist between these scores. The most popular score appears to be the PESI and its simplified version. Few good quality studies have tested the applicability of these scores to PE outpatient care, although this approach tends to already generalize in the medical practice.

  10. Glioblastoma treated with postoperative radio-chemotherapy: Prognostic value of apparent diffusion coefficient at MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Fumiyuki; Sugiyama, Kazuhiko [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Ohtaki, Megu [Department of Environmetrics and Biometrics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima (Japan); Takeshima, Yukio [Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Abe, Nobukazu; Akiyama, Yuji; Takaba, Junko [Department of Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Amatya, Vishwa Jeet [Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima (Japan); Saito, Taiichi; Kajiwara, Yoshinori; Hanaya, Ryosuke [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan); Kurisu, Kaoru [Department of Neurosurgery, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551 (Japan)], E-mail: kuka422@hiroshima-u.ac.jp

    2010-03-15

    Purpose: To retrospectively evaluate whether the mean, minimum, and maximum apparent diffusion coefficient (ADC) of glioblastomas obtained from pretreatment MR images is of prognostic value in patients with glioblastoma. Materials and methods: The institutional review board approved our study and waived the requirement for informed patient consent. Between February 1998 and January 2006, 33 patients (24 males, 9 females; age range 10-76 years) with supratentorial glioblastoma underwent pretreatment magnetic resonance (MR) imaging. The values of the mean, minimum, and maximum ADC (ADC{sub mean}, ADC{sub MIN}, and ADC{sub MAX}, respectively) of each tumor were preoperatively determined from several regions of interest defined in the tumors. After surgical intervention, all patients underwent irradiation and chemotherapy performed according to our hospital protocol. The patient age, symptom duration, Karnofsky performance scale score, extent of surgery, and ADC were assessed using factor analysis of overall survival. Prognostic factors were evaluated using Kaplan-Meier survival curves, the log-rank test, and multiple regression analysis with the Cox proportional hazards model. Results: Likelihood ratio tests confirmed that ADC{sub MIN} was the strongest among the three prognostic factors. Total surgical removal was the most important predictive factor for overall survival (P < 0.01). ADC{sub MIN} was also statistically correlated with overall survival (P < 0.05) and could be used to classify patients into different prognostic groups. Interestingly, ADC{sub MIN} was also the strongest prognostic factor (P < 0.01) in the group of patients in whom total tumor removal was not possible. Conclusion: The ADC{sub MIN} value obtained from pretreatment MR images is a useful clinical prognostic biomarker in patients with glioblastoma.

  11. An update on current management of advanced renal cell cancer, biomarkers, and future directions

    OpenAIRE

    Zhi, Wanqing Iris; Kim, Jenny J.

    2014-01-01

    In the past decade, metastatic renal cell carcinoma (mRCC) treatment underwent significant advancement that resulted in an unprecedented improvement in the prognosis of this disease. This review will provide an updated review of currently approved treatment options, namely antiangiogenic and immunotherapy, as well as treatment guideline recommended by the National Comprehensive Cancer Network (NCCN). We will summarize studies ongoing in determining prognostic and predictive biomarkers in maxi...

  12. Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

    KAUST Repository

    Mansour, Hicham

    2014-09-11

    The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

  13. Composite Biomarkers For Non-invasive Screening, Diagnosis And Prognosis Of Colorectal Cancer

    KAUST Repository

    Mansour, Hicham; Incitti, Roberto; Bajic, Vladimir B.

    2014-01-01

    The present invention concerns particular biomarkers for diagnosing and/or prognosticating colorectal cancer, in particular in a non-invasive manner. The methods and compositions concern analysis of methylation patterns of one or more genes from a set of 29 genes identified as described herein. In certain embodiments, the gene set includes at least P15.INK4b, SST, GAS7, CNRIP1, and PIK3CG.

  14. Current status on microRNAs as biomarkers for ovarian cancer

    DEFF Research Database (Denmark)

    Prahm, Kira Philipsen; Novotny, Guy Wayne; Høgdall, Claus

    2016-01-01

    Ovarian cancer (OC) is the most lethal gynecological malignancy in the Western world, and has a very poor prognosis, often due to late diagnosis and emergence of chemotherapy resistance. Therefore, there is an essential need for new diagnostic and prognostic markers that can improve and initiate ......RNAs in different types of OC. In this review we summarize the current knowledge of microRNAs as potential biomarkers for OC, with focus on their clinical relevance....

  15. Multimodality therapy and prognostic analysis of thymoma

    International Nuclear Information System (INIS)

    Chen Jie; Wang Ping; Song Yongchun

    2007-01-01

    Objective: The aim of this study is to draft the judicious treatment methods by analyzing the Long-term survival result of thymoma and evaluating the effect that prognosis analysis has on thymoma. Methods: Retrospective analysis of the clinical material of 142 patients with thymoma in the Tianjin Medical University Cancer Hospital from January 1954 to January 2001. Statistical analysis was performed using the SPSS software package. The Kaplan-Meier method was used single variable analysis, The Log-rank test was used to compare survival between groups, The Cox' s proportional hazards model was used to multi-factor analysis. Results: The 5- and 10-year survival rate of the 142 patients was 59.9% and 45.8%, respectively. Staging was adopted on the Masaoka's way, 5- and 10-year survival rates was: 93.8%, 79.2% in stage I; 79.3%, 55.2% in stage II; 53.1%, 34.4% in stage III; and 0 and 0 in stage IV. Among 30 patients associated with myasthenia gravis, 19 patients suffered from generalized myasthenia gravis and 11 patients of ocular myasthenia gravis, with 5- and 10-year survival rate of 83.3% and 60.0%, respectively. Three patients finally died of myasthenia gravis. The 5- and 10-year survival rate of 112 patients without myasthenia gravis was 53.6% and 42.0%, respectively. Among 116 patients, treated with surgery-, resection was carried out in 84 patients, palliative resection in 9 patients, and biopsy only in 23 patients. Eighty-nine patients were given radiotherapy and 55 patients had postoperative radiotherapy. Single variable analysis showed that Masaoka clinical staging, association with myasthenia gravis, histopathologic subtype and the method of treatment were prognostic factor's. Finally, drawing the conclusion through muhivariable analysis; Masaoka clinical staging, association with myasthenia gravis and the treatment method were prognostic factors. Conclusions: The diagnosis of thymoma is made clinically and pathologically. The treatment principle should be

  16. Candidate proteomic biomarkers for non-alcoholic fatty liver disease (steatosis and non-alcoholic steatohepatitis) discovered with mass-spectrometry: a systematic review.

    Science.gov (United States)

    Lădaru, Anca; Bălănescu, Paul; Stan, Mihaela; Codreanu, Ioana; Anca, Ioana Alina

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by lipid accumulation in the liver which is accompanied by a series of metabolic deregulations. There are sustained research efforts focusing upon biomarker discovery for NAFLD diagnosis and its prognosis in order investigate and follow-up patients as minimally invasive as possible. The objective of this study is to critically review proteomic studies that used mass spectrometry techniques and summarize relevant proteomic NAFLD candidate biomarkers. Medline and Embase databases were searched from inception to December 2014. A final number of 22 records were included that identified 251 candidate proteomic biomarkers. Thirty-three biomarkers were confirmed - 14 were found in liver samples, 21 in serum samples, and two from both serum and liver samples. Some of the biomarkers identified have already been extensively studied regarding their diagnostic and prognostic capacity. However, there are also more potential biomarkers that still need to be addressed in future studies.

  17. Prognostic radiographic aspects of spondylolisthesis

    International Nuclear Information System (INIS)

    Saraste, H.; Brostroem, L.A.; Aparisi, T.

    1984-01-01

    A series of 202 patients (133 men, 69 women) with lumbar spondylolysis were examined radiographically on two occasions, first at the time of diagnosis and later at a follow-up, after an observation period of 20 years or more. The films frompatients in groups without and with moderate and severe olisthesis were evaluated with respect to variables describing lumbosacral lordosis, wedging of the spondylolytic vertebra, lengths of the transverse processes and iliolumbar ligaments, disk height, progression of slipping, and influence on measured olisthesis of lumbar spine flexion and extension at the radiographic examination. The evaluation was made with special attention to possible signs which could be predictive for the prognosis of vertebral slipping. Progression of slipping did not differ between patients diagnosed as adults or adolescents. Reduction of disk height was correlated to the degree of slipping present at the initial examination and to the progression of olisthesis. Flexion and extension of the lumbar spine did not modify the degree of olisthesis. Data concerning the lengths of the transverse processes and the iliolumbar ligaments, and lumbar lordosis, cannot be used for prognostic purposes. The lumbar index reflecting the degree of wedge deformity of the spondylolytic vertebra was shown to be the only variable of prognostic value for the development of vertebral slipping. (orig.)

  18. Prognostic radiographic aspects of spondylolisthesis

    Energy Technology Data Exchange (ETDEWEB)

    Saraste, H; Brostroem, L A; Aparisi, T

    1984-01-01

    A series of 202 patients (133 men, 69 women) with lumbar spondylolysis were examined radiographically on two occasions, first at the time of diagnosis and later at a follow-up, after an observation period of 20 years or more. The films from patients in groups without and with moderate and severe olisthesis were evaluated with respect to variables describing lumbosacral lordosis, wedging of the spondylolytic vertebra, lengths of the transverse processes and iliolumbar ligaments, disk height, progression of slipping, and influence on measured olisthesis of lumbar spine flexion and extension at the radiographic examination. The evaluation was made with special attention to possible signs which could be predictive for the prognosis of vertebral slipping. Progression of slipping did not differ between patients diagnosed as adults or adolescents. Reduction of disk height was correlated to the degree of slipping present at the initial examination and to the progression of olisthesis. Flexion and extension of the lumbar spine did not modify the degree of olisthesis. Data concerning the lengths of the transverse processes and the iliolumbar ligaments, and lumbar lordosis, cannot be used for prognostic purposes. The lumbar index reflecting the degree of wedge deformity of the spondylolytic vertebra was shown to be the only variable of prognostic value for the development of vertebral slipping.

  19. Prognostic factors in Fournier gangrene.

    Science.gov (United States)

    Ruiz-Tovar, Jaime; Córdoba, Luis; Devesa, Jose Manuel

    2012-01-01

    Fournier gangrene is a necrotizing fasciitis, arising in the genital and perineal area. This entity is still associated with a high mortality rate despite improvements in antibiotic and surgical treatment. This is a retrospective study of all the patients diagnosed and surgically treated for Fournier gangrene at General University Hospital Ramon y Cajal between 1988 and 2008. Possible prognostic factors that could have any influence on the evolution of Fournier gangrene were analyzed. Seventy patients were analyzed, 62 males (88.6%) and 8 females (11.4%) with a mean age of 57.9 ± 13.5 years. Most frequent clinical manifestations were perineal pain (82.9%) and fever (60%). Physical examination revealed edema (91.4%), erythema (88.6%) and perineal skin necrosis (60%). All the patients underwent surgical debridement of necrotic tissue. In 54.3% reoperations were necessary for new surgical debridements. Medical complications rate was 27.1% and mortality one 22.9%. Ethylism, coexistence of neoplasms, presence of skin necrosis, myonecrosis, abdominal wall affection, number of debrided areas, reoperations, concentration of creatinine in serum>1.4 mg/dL, and hemoglobin <10 g/dL, and platelet count <150 × 10(9)/L in whole blood are associated with higher mortality rates. Identification of prognostic factors may help to determine high-risk patients in order to establish an optimal treatment, according to severity of the infection and general status. Copyright © 2012. Published by Elsevier B.V.

  20. [Biomarkers of Alzheimer disease].

    Science.gov (United States)

    Rachel, Wojciech; Grela, Agatha; Zyss, Tomasz; Zieba, Andrzej; Piekoszewski, Wojciech

    2014-01-01

    Cognitive impairment is one of the most abundant age-related psychiatric disorders. The outcome of cognitive impairment in Alzheimer's disease has both individual (the patients and their families) and socio-economic effects. The prevalence of Alzheimer's disease doubles after the age of 65 years, every 4.5 years. An etiologically heterogenic group of disorders related to aging as well as genetic and environmental interactions probably underlie the impairment in Alzheimer's disease. Those factors cause the degeneration of brain tissue which leads to significant cognitive dysfunction. There are two main hypotheses that are linked to the process of neurodegeneration: (i) amyloid cascade and (ii) the role of secretases and dysfunction of mitochondria. From the therapeutic standpoint it is crucial to get an early diagnosis and start with an adequate treatment. The undeniable progress in the field of biomarker research should lead to a better understanding of the early stages of the disorder. So far, the best recognised and described biomarkers of Alzheimer's disease, which can be detected in both cerebrospinal fluid and blood, are: beta-amyloid, tau-protein and phosphorylated tau-protein (phospho-tau). The article discusses the usefulness of the known biomarkers of Alzheimer's disease in early diagnosis.

  1. Prognostic, predictive and pharmacogenomic assessments of CDX2 refine stratification of colorectal cancer.

    Science.gov (United States)

    Bruun, Jarle; Sveen, Anita; Barros, Rita; Eide, Peter W; Eilertsen, Ina; Kolberg, Matthias; Pellinen, Teijo; David, Leonor; Svindland, Aud; Kallioniemi, Olli; Guren, Marianne G; Nesbakken, Arild; Almeida, Raquel; Lothe, Ragnhild A

    2018-06-14

    We aimed to refine the value of CDX2 as an independent prognostic and predictive biomarker in colorectal cancer (CRC) according to disease stage and chemotherapy sensitivity in preclinical models. CDX2 expression was evaluated in 1045 stage I-IV primary CRCs by gene expression (n=403) or immunohistochemistry (n=642) and in relation to 5-year relapse-free survival (RFS), overall survival (OS), and chemotherapy. Pharmacogenomic associations between CDX2 expression and 69 chemotherapeutics were assessed by drug screening of 35 CRC cell lines. CDX2 expression was lost in 11.6% of cases and showed independent poor prognostic value in multivariable models. For individual stages, CDX2 was prognostic only in stage IV, independent of chemotherapy. Among stage I-III patients not treated in an adjuvant setting, CDX2 loss was associated with a particularly poor survival in the BRAF-mutated subgroup, but prognostic value was independent of microsatellite instability status and the consensus molecular subtypes In stage III, the 5-year RFS rate was higher among patients with loss of CDX2 who received adjuvant chemotherapy than among patients who did not. The CDX2-negative cell lines were significantly more sensitive to chemotherapeutics than CDX2-positive cells, and the multidrug resistance genes MDR1 and CFTR were significantly downregulated both in CDX2-negative cells and patient tumors. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

  2. Breast MR imaging: correlation of high resolution dynamic MR findings with prognostic factors

    International Nuclear Information System (INIS)

    Lee, Shin Ho; Cho, Nariya; Chung, Hye Kyung; Kim, Seung Ja; Cho, Kyung Soo; Moon, Woo Kyung; Cho, Joo Hee

    2005-01-01

    We wanted to correlate the kinetic and morphologic MR findings of invasive breast cancer with the classical and molecular prognostic factors. Eighty-seven patients with invasive ductal carcinoma NOS underwent dynamic MR imaging at 1.5 T, and with using the T1-weighted 3D FLASH technique. The morphologic findings (shape, margin, internal enhancement of the mass or the enhancement distribution and the internal enhancement of any non-mass lesion) and the kinetic findings (the initial phase and the delayed phase of the time-signal. Intensity curve) were interpreted using a ACR BI-RADS-MRI lexicon. We correlate MR findings with histopathologic prognostic factors (tumor size, lymph node status and tumor grade) and the immunohistochemically detected biomarkers (ER, PR, ρ 53, c-erbB-2, EGFR and Ki-67). Univariate and multivariate statistical analyses were than performed. Among the MR findings, a spiculated margin, rim enhancement and washout were significantly correlated with the prognostic factors. A spiculated margin was independently associated with the established predictors of a good prognosis (a lower histologic and nuclear grade, positive ER and PR) and rim enhancement was associated with a poor prognosis (a higher histologic and nuclear grade, negative ER and PR). Wash out was a independent predictor of Ki-67 activity. Some of the findings of high resolution dynamic MR imaging were associated with the prognostic factors, and these findings may predict the prognosis of breast cancer

  3. Concordance for prognostic models with competing risks

    DEFF Research Database (Denmark)

    Wolbers, Marcel; Blanche, Paul; Koller, Michael T

    2014-01-01

    The concordance probability is a widely used measure to assess discrimination of prognostic models with binary and survival endpoints. We formally define the concordance probability for a prognostic model of the absolute risk of an event of interest in the presence of competing risks and relate i...

  4. Shotgun Proteomics and Biomarker Discovery

    Directory of Open Access Journals (Sweden)

    W. Hayes McDonald

    2002-01-01

    Full Text Available Coupling large-scale sequencing projects with the amino acid sequence information that can be gleaned from tandem mass spectrometry (MS/MS has made it much easier to analyze complex mixtures of proteins. The limits of this “shotgun” approach, in which the protein mixture is proteolytically digested before separation, can be further expanded by separating the resulting mixture of peptides prior to MS/MS analysis. Both single dimensional high pressure liquid chromatography (LC and multidimensional LC (LC/LC can be directly interfaced with the mass spectrometer to allow for automated collection of tremendous quantities of data. While there is no single technique that addresses all proteomic challenges, the shotgun approaches, especially LC/LC-MS/MS-based techniques such as MudPIT (multidimensional protein identification technology, show advantages over gel-based techniques in speed, sensitivity, scope of analysis, and dynamic range. Advances in the ability to quantitate differences between samples and to detect for an array of post-translational modifications allow for the discovery of classes of protein biomarkers that were previously unassailable.

  5. Investigating a multigene prognostic assay based on significant pathways for Luminal A breast cancer through gene expression profile analysis.

    Science.gov (United States)

    Gao, Haiyan; Yang, Mei; Zhang, Xiaolan

    2018-04-01

    The present study aimed to investigate potential recurrence-risk biomarkers based on significant pathways for Luminal A breast cancer through gene expression profile analysis. Initially, the gene expression profiles of Luminal A breast cancer patients were downloaded from The Cancer Genome Atlas database. The differentially expressed genes (DEGs) were identified using a Limma package and the hierarchical clustering analysis was conducted for the DEGs. In addition, the functional pathways were screened using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses and rank ratio calculation. The multigene prognostic assay was exploited based on the statistically significant pathways and its prognostic function was tested using train set and verified using the gene expression data and survival data of Luminal A breast cancer patients downloaded from the Gene Expression Omnibus. A total of 300 DEGs were identified between good and poor outcome groups, including 176 upregulated genes and 124 downregulated genes. The DEGs may be used to effectively distinguish Luminal A samples with different prognoses verified by hierarchical clustering analysis. There were 9 pathways screened as significant pathways and a total of 18 DEGs involved in these 9 pathways were identified as prognostic biomarkers. According to the survival analysis and receiver operating characteristic curve, the obtained 18-gene prognostic assay exhibited good prognostic function with high sensitivity and specificity to both the train and test samples. In conclusion the 18-gene prognostic assay including the key genes, transcription factor 7-like 2, anterior parietal cortex and lymphocyte enhancer factor-1 may provide a new method for predicting outcomes and may be conducive to the promotion of precision medicine for Luminal A breast cancer.

  6. Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

    Science.gov (United States)

    Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

    2017-05-31

    BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

  7. Prognostic value of pretreatment albumin/globulin ratio in digestive system cancers: A meta-analysis.

    Science.gov (United States)

    Guo, Hui-Wen; Yuan, Tang-Zhan; Chen, Jia-Xi; Zheng, Yang

    2018-01-01

    The albumin/globulin ratio (AGR) has been widely reported to be a potential predictor of prognosis in digestive system cancers (DSCs), but convincing conclusions have not been made. Therefore, herein, we performed a meta-analysis of relevant studies regarding this topic to evaluate the prognostic value of AGR in patients with DSCs. Three databases, including PubMed, EMBase, and Web of science, were searched comprehensively for eligible studies through September 8, 2017. The outcomes of interest included overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS). In our meta-analysis, pooled analysis of 13 studies with 9269 patients showed that a low AGR was significantly correlated with poor OS (HR = 1.94; 95% CI: 1.57-2.38; P digestive system cancers. A low pretreatment AGR may be a useful predictive prognostic biomarker in human digestive system cancers.

  8. Biomarkers in Diabetic Retinopathy

    Science.gov (United States)

    Jenkins, Alicia J.; Joglekar, Mugdha V.; Hardikar, Anandwardhan A.; Keech, Anthony C.; O'Neal, David N.; Januszewski, Andrzej S.

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  9. Biomarkers in Diabetic Retinopathy.

    Science.gov (United States)

    Jenkins, Alicia J; Joglekar, Mugdha V; Hardikar, Anandwardhan A; Keech, Anthony C; O'Neal, David N; Januszewski, Andrzej S

    2015-01-01

    There is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat

  10. Prognostic and predictive biomarkers for hypoxic regions on breast cancer: advances and challenges Biomarcadores preditivos e prognósticos em regiões hipóxicas do câncer de mama: avanços e desafios

    Directory of Open Access Journals (Sweden)

    Moacyr Jesus Barreto de Melo Rêgo

    2013-02-01

    Full Text Available Hypoxia has been extensively studied in solid tumors mainly in breast cancers and it is commonly associated with chemotherapy and radiotherapy resistance. Hypoxia inducible factor (HIF-1α is responsible for hypoxia in the tumor microenvironment and its molecular mechanisms as well as its therapeutic strategies have been described. However, a few investigations in the literature deal with its role in the hypoxic environment at diagnosis with the aim to guide therapeutic approaches. This study alerts researchers in pathology and oncology to the importance of assessing area extension as well as specific biomarkers, inasmuch as molecules reactive to hypoxia may indicate response to antiangiogenic therapy. The extension of hypoxic areas may alter the choice of therapeutic approach, insofar as some antiangiogenic treatments may considerably aggravate patient's clinical course since they create a hypoxic environment.A hipóxia vem sendo bastante estudada nos tumores sólidos, principalmente nos de mama, os quais são frequentemente responsáveis pela resistência a quimioterapia e radioterapia. O hypoxia inducible factor (HIF-1α é o principal responsável pela hipóxia no microambiente tumoral e seus mecanismos moleculares têm sido descritos, além de estratégias terapêuticas desenhadas para essa molécula. Porém, poucos estudos na literatura tratam do papel do microambiente hipóxico no momento do diagnóstico para colaborar com a conduta dos oncologistas. Este artigo alerta os pesquisadores em patologia e oncologia para que eles observem a importância da avaliação da extensão da área, bem como dos biomarcadores específicos para esse ambiente, já que moléculas responsivas à hipóxia podem ser indicativas de resposta à terapia antiangiogênica. A extensão das áreas hipóxicas pode mudar a decisão do oncologista na escolha da conduta terapêutica, visto que alguns tratamentos antiangiogênicos podem piorar consideravelmente a evolu

  11. Prognostic value of tumor suppressors in osteosarcoma before and after neoadjuvant chemotherapy.

    Science.gov (United States)

    Robl, Bernhard; Pauli, Chantal; Botter, Sander Martijn; Bode-Lesniewska, Beata; Fuchs, Bruno

    2015-05-09

    Primary bone cancers are among the deadliest cancer types in adolescents, with osteosarcomas being the most prevalent form. Osteosarcomas are commonly treated with multi-drug neoadjuvant chemotherapy and therapy success as well as patient survival is affected by the presence of tumor suppressors. In order to assess the prognostic value of tumor-suppressive biomarkers, primary osteosarcoma tissues were analyzed prior to and after neoadjuvant chemotherapy. We constructed a tissue microarray from high grade osteosarcoma samples, consisting of 48 chemotherapy naïve biopsies (BXs) and 47 tumor resections (RXs) after neoadjuvant chemotherapy. We performed immunohistochemical stainings of P53, P16, maspin, PTEN, BMI1 and Ki67, characterized the subcellular localization and related staining outcome with chemotherapy response and overall survival. Binary logistic regression analysis was used to analyze chemotherapy response and Kaplan-Meier-analysis as well as the Cox proportional hazards model was applied for analysis of patient survival. No significant associations between biomarker expression in BXs and patient survival or chemotherapy response were detected. In univariate analysis, positive immunohistochemistry of P53 (P = 0.008) and P16 (P16; P = 0.033) in RXs was significantly associated with poor survival prognosis. In addition, presence of P16 in RXs was associated with poor survival in multivariate regression analysis (P = 0.003; HR = 0.067) while absence of P16 was associated with good chemotherapy response (P = 0.004; OR = 74.076). Presence of PTEN on tumor RXs was significantly associated with an improved survival prognosis (P = 0.022). Positive immunohistochemistry (IHC) of P16 and P53 in RXs was indicative for poor overall patient survival whereas positive IHC of PTEN was prognostic for good overall patient survival. In addition, we found that P16 might be a marker of osteosarcoma chemotherapy resistance. Therefore, our study supports the use of tumor RXs to

  12. The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

    Science.gov (United States)

    Cox, Samantha; Hurt, Christopher; Grenader, Tal; Mukherjee, Somnath; Bridgewater, John; Crosby, Thomas

    2017-10-01

    The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479]. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. The Prognostic Value of Haplotypes in the Vascular Endothelial Growth Factor A Gene in Colorectal Cancer

    International Nuclear Information System (INIS)

    Hansen, Torben F.; Spindler, Karen-Lise G.; Andersen, Rikke F.; Lindebjerg, Jan; Kølvraa, Steen; Brandslund, Ivan; Jakobsen, Anders

    2010-01-01

    New prognostic markers in patients with colorectal cancer (CRC) are a prerequisite for individualized treatment. Prognostic importance of single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGF-A) gene has been proposed. The objective of the present study was to investigate the prognostic importance of haplotypes in the VEGF-A gene in patients with CRC. The study included 486 patients surgically resected for stage II and III CRC, divided into two independent cohorts. Three SNPs in the VEGF-A gene were analyzed by polymerase chain reaction. Haplotypes were estimated using the PHASE program. The prognostic influence was evaluated using Kaplan-Meir plots and log rank tests. Cox regression method was used to analyze the independent prognostic importance of different markers. All three SNPs were significantly related to survival. A haplotype combination, responsible for this effect, was present in approximately 30% of the patients and demonstrated a significant relationship with poor survival, and it remained an independent prognostic marker after multivariate analysis, hazard ratio 2.46 (95% confidence interval 1.49–4.06), p < 0.001. Validation was provided by consistent findings in a second and independent cohort. Haplotype combinations call for further investigation

  14. Prognostic significance of anaplasia and angiogenesis in childhood medulloblastoma: a pediatric oncology group study.

    Science.gov (United States)

    Ozer, Erdener; Sarialioglu, Faik; Cetingoz, Riza; Yüceer, Nurullah; Cakmakci, Handan; Ozkal, Sermin; Olgun, Nur; Uysal, Kamer; Corapcioglu, Funda; Canda, Serefettin

    2004-01-01

    The purpose of this study was to investigate whether quantitative assessment of cytologic anaplasia and angiogenesis may predict the clinical prognosis in medulloblastoma and stratify the patients to avoid both undertreatment and overtreatment. Medulloblastomas from 23 patients belonging to the Pediatric Oncology Group were evaluated with respect to some prognostic variables, including histologic assessment of nodularity and desmoplasia, grading of anaplasia, measurement of nuclear size, mitotic cell count, quantification of angiogenesis, including vascular surface density (VSD) and microvessel number (NVES), and immunohistochemical scoring of vascular endothelial growth factor (VEGF) expression. Univariate and multivariate analyses for prognostic indicators for survival were performed. Univariate analysis revealed that extensive nodularity was a significant favorable prognostic factor, whereas the presence of anaplasia, increased nuclear size, mitotic rate, VSD, and NVES were significant unfavorable prognostic factors. Using multivariate analysis, increased nuclear size was found to be an independent unfavorable prognostic factor for survival. Neither the presence of desmoplasia nor VEGF expression was significantly related to patient survival. Although care must be taken not to overstate the importance of the results of this single-institution preliminary report, pathologic grading of medulloblastomas with respect to grading of anaplasia and quantification of nodularity, nuclear size, and microvessel profiles may be clinically useful for the treatment of medulloblastomas. Further validation of the independent prognostic significance of nuclear size in stratifying patients is required.

  15. [An analysis of 68 invasive lobular breast cancer cases in clinicopathological characteristics and the prognostic determinants].

    Science.gov (United States)

    Liu, Q; Xiang, H Y; Ye, J M; Xu, L; Zhang, H; Zhang, S; Duan, X N; Liu, Y H

    2018-02-01

    Objective: To study the clinicopathological characteristics and the prognostic determinants of the invasive lobular carcinoma breast cancer. Methods: This was a retrospective single-center study of invasive lobular breast cancer cases diagnosed from January 2008 to December 2014 at Peking University First Hospital Breast Disease Center. The study enrolled 68 invasive lobular breast cancer patients, which represented 3.64% (68/1 870) of total invasive breast cancer. The median age of all selected patients was 46 years ranging from 36 to 83 years. All patients were restaged based on the 8(th) edition of AJCC cancer staging system and follow-up data including disease-free survival (DFS) and overall survival (OS) were analyzed to explore the prognostic determinants. The 5-year OS and DFS were calculated using Kaplan-Meier method; the significance of correlations between clinicopathological features and prognostic factors was estimated using log-rank test. Results: There were significant differences in OS between patients with different anatomic stage, prognostic stage, lymph node metastasis, progesterone receptor (PR) expression, lymphvascular invasion and perineural invasion (χ(2:) 4.318 to 32.394, all P invasion (χ(2:) 4.347 to 27.369, all P invasion are the prognostic factors of invasive lobular breast cancer. Regard to invasive lobular breast cancer patients, clinicians should pay close attention to the differences between prognostic stage and anatomic stage.

  16. Predictive Biomarkers for Asthma Therapy.

    Science.gov (United States)

    Medrek, Sarah K; Parulekar, Amit D; Hanania, Nicola A

    2017-09-19

    Asthma is a heterogeneous disease characterized by multiple phenotypes. Treatment of patients with severe disease can be challenging. Predictive biomarkers are measurable characteristics that reflect the underlying pathophysiology of asthma and can identify patients that are likely to respond to a given therapy. This review discusses current knowledge regarding predictive biomarkers in asthma. Recent trials evaluating biologic therapies targeting IgE, IL-5, IL-13, and IL-4 have utilized predictive biomarkers to identify patients who might benefit from treatment. Other work has suggested that using composite biomarkers may offer enhanced predictive capabilities in tailoring asthma therapy. Multiple biomarkers including sputum eosinophil count, blood eosinophil count, fractional concentration of nitric oxide in exhaled breath (FeNO), and serum periostin have been used to identify which patients will respond to targeted asthma medications. Further work is needed to integrate predictive biomarkers into clinical practice.

  17. Biomarkers for the Diagnosis of Cholangiocarcinoma: A Systematic Review.

    Science.gov (United States)

    Tshering, Gyem; Dorji, Palden Wangyel; Chaijaroenkul, Wanna; Na-Bangchang, Kesara

    2018-06-01

    Cholangiocarcinoma (CCA), a malignant tumor of the bile duct, is a major public health problem in many Southeast Asian countries, particularly Thailand. The slow progression makes it difficult for early diagnosis and most patients are detected in advanced stages. This study aimed to review all relevant articles related to the biomarkers for the diagnosis of CCA and point out potential biomarkers. A thorough search was performed in PubMed and ScienceDirect for CCA biomarker articles. Required data were extracted. A total of 46 articles that fulfilled the inclusion and had none of the exclusion criteria were included in the analysis (17, 22, 3, 4, and 1 articles on blood, tissue, bile, both blood and tissue, and urine biomarkers, respectively). Carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA), either alone or in combination with other biomarkers, are the most commonly studied biomarkers in the serum. Their sensitivity and specificity ranged from 47.2% to 98.2% and 89.7% to 100%, respectively. However, in the tissue, gene methylations and DNA-related markers were the most studied CCA biomarkers. Their sensitivity and specificity ranged from 58% to 87% and 98% to 100%, respectively. Some articles investigated biomarkers both in blood and tissues, particularly CA19-9 and CEA, with sensitivity and specificity ranging from 33% to 100% and 50% to 97.7%, respectively. Although quite a number of biomarkers with a potential role in the early detection of CCA have been established, it is difficult to single out any particular marker that could be used in the routine clinical set