Abstract 2873: A molecular signature predictive of indolent prostate cancer

Abstract

Abstract With more than 230,000 estimated new cases in 2013, prostate cancer represents the most commonly diagnosed cancer in American men. While a subgroup of patients will develop an aggressive and lethal prostate cancer, most present with a low-risk form of the disease that requires little or no treatment. It is therefore crucial to distinguish patients whose tumors are likely to progress to aggressive disease from those whose tumors will remain indolent and for whom treatment may be more detrimental than beneficial. In our recent study, we hypothesized that low Gleason score prostate tumors can be distinguished as indolent and aggressive based on expression of genes associated with aging and senescence (1). Using gene set enrichment analyses and a decision tree learning model, we identified a 3-gene panel_FGFR1, PMP22, and CDKN1A_that is enriched in indolent prostate cancers and accurately predicts outcome of low Gleason score tumors at both the RNA and protein levels. In particular, protein expression of this 3-gene panel in biopsy samples correctly distinguished Gleason 6 patients who failed active surveillance over a 10-year period. Following from our initial study, our current efforts are focused on exploiting this 3-gene panel to develop a robust clinical assay for distinguishing indolent and aggressive tumors. We are currently using qRT-PCR, immunofluorescence, and immunohistochemistry assays to assess the most effective way to quantify the simultaneous expression of the 3-gene panel in low Gleason score tumor biopsies/tissues. This quantitative assay will ultimately be applied to a large cohort study assessing the predictive power of the 3-gene signature in patients under active surveillance. We envision that such a prognostic test will significantly improve our ability to predict the outcome of patients with low Gleason score tumors and facilitate appropriate decisions of treatment for men under active surveillance. 1. Irshad S, et al. (2013) A molecular signature predictive of indolent prostate cancer. Science translational medicine 5(202):202ra122. Citation Format: Shazia Irshad, Mukesh Bansal, Clementine Le Magnen, Risham Dillon, Mireia Castillo-Martin, Tian Zheng, Alvaro Aytes, Sven Wenske, Paolo Guarnieri, Pavel Sumazin, Mitchell Benson, Michael M. Shen, Andrea Califano, Cory Abate-Shen. A molecular signature predictive of indolent prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2873. doi:10.1158/1538-7445.AM2014-2873