Prostate carcinoma in African-Americans has miRNA expression and biological markers for aggressive disease.

Abstract

e16558 Background: African American (AA) men have twice the incidence and mortality in Prostate Cancer (PCa) as compared to non-Hispanic Whites. The identification of a biological basis for this disparity is crucial in providing focused treatment. In this study, we have characterized the pathological features and molecular markers of PCa in AA men. Methods: 91 proctectomies for primary PCa and 23 biopsies for metastatic PCa with their pathological data were retrieved. Tissue microarrays were constructed and the expression of Programmed Cell Death 1 (PD-1), Programmed Death Ligand 1 (PD-L1) and Mismatch Repair (MMR) (MLH1, MSH2, MSH6 and PMS2) proteins was assessed by immunohistochemistry. miRNA expression of 24 cases of primary PCa and adjacent normal prostate tissue from proctectomies was identified by microarray in situ hybridization. Spearman’s rank-correlation was used to correlate variables and p < .05 was considered significant. TargetScan and DIANA analysis software were used to identify modulation in miRNA expression. Results: In a supervised heat map, overall the downregulation of microRNA was more than upregulation in tumor tissue; 11 miRNA were upregulated and 12 were downregulated, with a log fold change of 1.5. miR-345, a component of the mismatch repair and DNA Replication pathway, showed significant up-regulation (p = 9.4E-02); has been linked to more aggressive PCa. PD-L1 expression was lower in primary PCa (16%) than in metastatic PCa (35%). PD-1 expression was high in almost half of primary and metastatic PCa patients. MMR protein expression was largely intact in both primary and metastatic PCa cases. Both of these protein markers have been associated with biochemical recurrence and low survival. Conclusions: The biological characteristics (low expression of PD-L1, high expression of PD-1, intact MMR and distinct miRNA signature) identified in our cohort of exclusively AA men are indicators of aggressive PCa. These results explain the biological basis of widely documented poor prognosis of PCa in AA men.