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      Antibody response to BK polyomavirus as a prognostic biomarker and potential therapeutic target in prostate cancer

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          Abstract

          Infectious agents, including the BK polyomavirus (BKPyV), have been proposed as important inflammatory pathogens in prostate cancer. Here, we evaluated whether the preoperative antibody response to BKPyV large T antigen (LTag) and viral capsid protein 1 (VP1) was associated with the risk of biochemical recurrence in 226 patients undergoing radical prostatectomy for primary prostate cancer. Essentially, the multivariate Cox regression analysis revealed that preoperative seropositivity to BKPyV LTag significantly reduced the risk of biochemical recurrence, independently of established predictors of biochemical recurrence such as tumor stage, Gleason score and surgical margin status. The predictive accuracy of the regression model was denotatively increased by the inclusion of the BKPyV LTag serostatus. In contrast, the VP1 serostatus was of no prognostic value. Finally, the BKPyV LTag serostatus was associated with a peculiar cytokine gene expression profile upon assessment of the cellular immune response elicited by LTag. Taken together, our findings suggest that the BKPyV LTag serology may serve as a prognostic factor in prostate cancer. If validated in additional studies, this biomarker may allow for better treatment decisions after radical prostatectomy. Finally, the favorable outcome of LTag seropositive patients may provide a potential opportunity for novel therapeutic approaches targeting a viral antigen.

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          Most cited references34

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          Estimating and comparing time-dependent areas under receiver operating characteristic curves for censored event times with competing risks.

          The area under the time-dependent ROC curve (AUC) may be used to quantify the ability of a marker to predict the onset of a clinical outcome in the future. For survival analysis with competing risks, two alternative definitions of the specificity may be proposed depending of the way to deal with subjects who undergo the competing events. In this work, we propose nonparametric inverse probability of censoring weighting estimators of the AUC corresponding to these two definitions, and we study their asymptotic properties. We derive confidence intervals and test statistics for the equality of the AUCs obtained with two markers measured on the same subjects. A simulation study is performed to investigate the finite sample behaviour of the test and the confidence intervals. The method is applied to the French cohort PAQUID to compare the abilities of two psychometric tests to predict dementia onset in the elderly accounting for death without dementia competing risk. The 'timeROC' R package is provided to make the methodology easily usable. Copyright © 2013 John Wiley & Sons, Ltd.
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            The 2005 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma.

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              Inflammation in prostate carcinogenesis.

              About 20% of all human cancers are caused by chronic infection or chronic inflammatory states. Recently, a new hypothesis has been proposed for prostate carcinogenesis. It proposes that exposure to environmental factors such as infectious agents and dietary carcinogens, and hormonal imbalances lead to injury of the prostate and to the development of chronic inflammation and regenerative 'risk factor' lesions, referred to as proliferative inflammatory atrophy (PIA). By developing new experimental animal models coupled with classical epidemiological studies, genetic epidemiological studies and molecular pathological approaches, we should be able to determine whether prostate cancer is driven by inflammation, and if so, to develop new strategies to prevent the disease.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                20 March 2015
                31 January 2015
                : 6
                : 8
                : 6459-6469
                Affiliations
                1 Oncology Research Unit, Division of Urology and Division of Surgical Research, University Hospital Zurich, CH-8091 Zurich, Switzerland
                2 Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, CH-4003 Basel, Switzerland
                3 Epidemiology, Biostatistics and Prevention Institute, University of Zurich, CH-8001 Zurich, Switzerland
                4 Infectious Diseases & Hospital Epidemiology, University Hospital Basel, CH-4031 Basel, Switzerland
                Author notes
                Correspondence to: Maurizio Provenzano, maurizio.provenzano@ 123456usz.ch
                Article
                4467449
                25749042
                631274d7-9a4d-4725-b4da-22aa71f5c9f2
                Copyright: © 2015 Keller et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 3 December 2014
                : 15 January 2015
                Categories
                Clinical Research Paper

                Oncology & Radiotherapy
                bk polyomavirus,prostate cancer,prognosis,antibody response,biochemical recurrence

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