Abstract 849: The changing role of GDF15 (growth/differentiation factor 15) during prostate carcinogenesis

Abstract

Abstract GDF15 (growth/differentiation factor 15) is a divergent member of the TGFβ superfamily of cytokines and is highly expressed in prostate tumors, but its role in prostate carcinogenesis and utility as a prognostic biomarker is unclear. We studied 58 prostate cancer cases (35 Whites and 23 African Americans) that underwent surgery as their primary treatment and were then subsequently followed for biochemical recurrence (BCR). In these cases, which also had a benign prostate biopsy at least one year before their prostate cancer diagnosis, we quantified GDF15 expression in their pre-malignant benign prostate, prostate tumor and tumor adjacent benign prostate tissue. GDF15 expression levels were analyzed for association with high grade prostate cancer and BCR. Twenty-six percent of cases had high grade cancer defined as Gleason score 8 or higher or a Gleason score of 7 and a primary Gleason of 4. During follow-up, 11 cases (19%) experienced BCR (80 percent of men without BCR had at least 2 years of follow-up). GDF15 expression was not associated high grade cancer in any prostate tissue types. GDF15 expression was associated with BCR, but the direction of the association was dependent upon the type of prostate tissue expression measured. Evidence of GDF15 expression in pre-malignant benign prostate was associated with an almost 9-fold increased risk of BCR (Hazard Ratio (HR) = 8.90; 95% confidence interval (CI) = 1.09-72.49), even after adjusting for race, tumor grade and stage. When we stratified men into low and high expression groups, we also found a significant gradient of risk with increased GDF15 expression (p = 0.03). The opposite was found for GDF15 expression in tumor tissue, where men with low GDF15 expression had a decreased risk of BCR (HR = 0.30; 95% CI = 0.06- 1.59), and men with high GDF15 expression were at an even lower risk (HR = 0.10; 95% CI = 0.02-0.61). Expression of GDF15 in tumor adjacent benign prostate tissue was not associated with BCR. The role GDF15 plays in prostate carcinogenesis is complex and may change during the course of tumor development. Our results suggest GDF15 exerts a pro-tumorgenic effect very early in prostate carcinogenesis, but later after the tumor becomes clinically apparent, GDF15 may act more in an anti-tumorgenic manner. Citation Format: Benjamin A. Rybicki, Dhananjay Chitale, Nilesh Gupta, LaToya Jackson, Travis Wheeler, Sheri Trudeau, Michelle Jankowski, Kevin Bobbittt, Andrew Rundle, Delian Tang. The changing role of GDF15 (growth/differentiation factor 15) during prostate carcinogenesis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 849. doi:10.1158/1538-7445.AM2015-849