Abstract B56: Regulation of CXCR5-CXCL13 signaling in prostate cancer etiologic disparities

Abstract

The prevalence of prostate cancer (PCa) has been a worldwide burden. Cancer of the prostate is the most prevalent form of cancer in men and the second leading cause of death due to cancer in men in the United States and Europe. There is a major health disparity associated with PCa; the number of fatalities associated with this disease is more significant in African-American (AA) men than in European American (EA) men. Disease progression occurs despite hormone ablation therapy, which leads to a condition called castration-resistant prostate cancer (CRPC). Further complicating the matter, CRPC is a disease that affects a variety of patients differently, which can be problematic for physicians to provide standardized treatments with similar outcomes. AAs with CRPC can experience significantly lower rates of overall survival, faster rates of tumor progression, and poor responses to chemotherapy compared to EAs with this disease. We previously showed that CXCL13:CXCR5 axis plays a role in PCa pathobiology and is also associated with PCa aggressiveness; CXCR5 signaling mediates PCa cell growth, migration, invasion, and docetaxel resistance. To further understand the implication of CXCR5-CXCL13 in CRPC, we characterize the reason behind the health disparities seen across groups of PCa patients by evaluating the difference in regulatory molecules (miRNAs) on CXCL13-CXCR5 signaling. We found the expression profile of CXCL13 and CXCR5 RNA to be associated with miRNAs (miR-140-3p.1, miR-24-3p, miR-200c, miR-221-3p/22-3p, miR-192-5p/215-5p, miR-214-5p). Using RNA-seq datasets from the Gene Expression Omnibus (GEO) and the Sequence Read Archive (SRA), CXCL13 and CXCR5 RNA as well as associated miRNAs (miR-140-3p.1, miR-24-3p, miR-221-3p/22-3p, miR-192-5p/215-5p, and miR-214-5p) were defined by etiologic disparities among PCa patients; this correlation is different among AA men compared to EA men. Understanding PCa and specifically CRPC disparities requires a better understanding of the race-specific differences in prostate tumor biology, molecules leading to prostate inflammation, and the mechanisms associated with CRPC therapeutic resistance and its aggressive phenotype. Citation Format: Adaugo Queen Ohandjo, Courtney Dill, Chen Dongquan, James W. Lillard, Jr.. Regulation of CXCR5-CXCL13 signaling in prostate cancer etiologic disparities [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B56.