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作为前列腺癌预后生物标志物和潜在治疗靶点的BK多瘤病毒抗体反应

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

作者信息

Keller Xavier Etienne, Kardas Piotr, Acevedo Claudio, Sais Giovanni, Poyet Cédric, Banzola Irina, Mortezavi Ashkan, Seifert Burkhardt, Sulser Tullio, Hirsch Hans H, Provenzano Maurizio

机构信息

Oncology Research Unit, Division of Urology and Division of Surgical Research, University Hospital Zurich, CH-8091 Zurich, Switzerland.

Transplantation and Clinical Virology, Department Biomedicine (Haus Petersplatz), University of Basel, CH-4003 Basel, Switzerland.

出版信息

Oncotarget. 2015 Mar 20;6(8):6459-69. doi: 10.18632/oncotarget.3363.

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.

摘要

包括BK多瘤病毒(BKPyV)在内的感染因子被认为是前列腺癌中重要的炎症病原体。在此,我们评估了226例因原发性前列腺癌接受根治性前列腺切除术患者术前对BKPyV大T抗原(LTag)和病毒衣壳蛋白1(VP1)的抗体反应是否与生化复发风险相关。本质上,多变量Cox回归分析显示,术前BKPyV LTag血清反应阳性显著降低了生化复发风险,这独立于生化复发的既定预测因素,如肿瘤分期、Gleason评分和手术切缘状态。回归模型的预测准确性因纳入BKPyV LTag血清状态而显著提高。相比之下,VP1血清状态没有预后价值。最后,在评估由LTag引发的细胞免疫反应时,BKPyV LTag血清状态与特定的细胞因子基因表达谱相关。综上所述,我们的研究结果表明,BKPyV LTag血清学可能作为前列腺癌的一个预后因素。如果在更多研究中得到验证,这种生物标志物可能有助于根治性前列腺切除术后做出更好的治疗决策。最后,LTag血清反应阳性患者的良好预后可能为针对病毒抗原的新型治疗方法提供潜在机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dac6/4467449/4d7b2bfb742c/oncotarget-06-6459-g001.jpg

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