Clinical Research Papers:
Antibody response to BK polyomavirus as a prognostic biomarker and potential therapeutic target in prostate cancer
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Abstract
Xavier Etienne Keller1, Piotr Kardas2, Claudio Acevedo1, Giovanni Sais1, Cédric Poyet1, Irina Banzola1, Ashkan Mortezavi1, Burkhardt Seifert3, Tullio Sulser1, Hans H. Hirsch2,4,* and Maurizio Provenzano1,*
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
* These authors contributed equally to this work
Correspondence:
Maurizio Provenzano, email:
Keywords: BK polyomavirus, prostate cancer, prognosis, antibody response, biochemical recurrence
Received: December 03, 2014 Accepted: January 15, 2015 Published: January 31, 2015
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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