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


Keller, Xavier Etienne; Kardas, Piotr; Acevedo, Claudio; Sais, Giovanni; Poyet, Cédric; Banzola, Irina; Mortezavi, Ashkan; Seifert, Burkhardt; Sulser, Tullio; Hirsch, Hans H; Provenzano, Maurizio (2015). Antibody response to BK polyomavirus as a prognostic biomarker and potential therapeutic target in prostate cancer. OncoTarget, 6(8):6459-6469.

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.

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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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Epidemiology, Biostatistics and Prevention Institute (EBPI)
04 Faculty of Medicine > University Hospital Zurich > Urological Clinic
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:31 January 2015
Deposited On:19 Mar 2015 09:24
Last Modified:05 Apr 2016 19:11
Publisher:Impact Journals, LLC
ISSN:1949-2553
Free access at:Official URL. An embargo period may apply.
Related URLs:http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3363
PubMed ID:25749042
Permanent URL: https://doi.org/10.5167/uzh-109968

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