Abstract 5716: Tristetraprolin is a prognostic biomarker for biochemical recurrence in low Gleason score patients

Abstract

Abstract PURPOSE: Most prostate cancer patients currently classified as having a low-risk of disease-specific death are overtreated in the United States, resulting in hundreds of thousands of men to have debilitating side effects from unnecessary treatment. However, ~30% of low-risk patients on active surveillance are later reclassified and require therapeutic intervention. Thus, there is a dire need for biomarkers that can discriminate which prostate tumors currently classified as low-risk will progress into aggressive disease. EXPERIMENTAL DESIGN: Retrospective analyses of two independent prostate cancer expression datasets were performed to determine the relationship between the expression levels of the tumor suppressor Tristetraprolin (TTP, ZFP36) and biochemical recurrence (BCR). Further, TTP expression levels were measured by quantitative real-time PCR (qRT-PCR) in a cohort of prostate tumors from Moffitt Cancer Center patients having long-term follow-up (n=382), and will be correlated to associated clinical data, including BCR. Finally, the Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) scores, a clinical tool used to predict prostate cancer outcomes following radical prostatectomy, were calculated along with BCR for the patients in one of the prostate cancer datasets. RESULTS: Analysis of The Cancer Genome Atlas (TCGA) prostate adenocarcinoma dataset revealed that tumors with low TTP expression have an increased rate of BCR compared to those with high TTP levels (p=0.0096). Further, assessment of the GEO dataset GSE21034 (Taylor et al., Cancer Cell, 2010) established that prostate cancer patients with low Gleason scores (6 and 3+4) have an increased chance of BCR if their tumors express low levels of TTP compared to men with high TTP expressing tumors (p=0.0001). To validate these findings, patients with low Gleason score tumors and decreased levels of TTP in the Moffitt Cancer Center cohort are being analyzed to determine their rate of BCR. In contrast, CAPRA-S scores for low Gleason score tumors in the GSE20134 dataset failed to distinguish if a patient would have BCR (p=0.0511). CONCLUSIONS: Prostate cancer patients with Gleason score 6 or 3+4, which are currently classified as having a low-risk of dying from prostate cancer, have an increased risk of BCR if their tumor expresses low levels of the tumor suppressor TTP. Our data suggests that TTP may be a biomarker that clearly discriminates which low Gleason score tumors will progress into aggressive disease. Citation Format: Anders E. Berglund, Travis Gerke, Shivanshu Awasthi, G. Daniel Grass, Hyun Y. Park, John L. Cleveland, Jong Y. Park, Kosj Yamoah, Robert J. Rounbehler. Tristetraprolin is a prognostic biomarker for biochemical recurrence in low Gleason score patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5716. doi:10.1158/1538-7445.AM2017-5716