Abstract B44: Exosomes-associated miR-3128 and miR-3613 are dysregulated in African American men with prostate cancer and correlated with poor prognosis

Abstract

Abstract Background: The mortality rate of prostate cancer (PCa) is two times higher in African American (AA) than in Caucasian American (CA) men. The molecular mechanisms underlying these discrepancies among AA men have yet to be fully elucidated. We aimed to evaluate the role of exosomes (Exo)-associated microRNAs (miR-3613 and miR-3128) as epigenetic determinant for the racial disparity of PCa patients. Methods: Exosomes were isolated from the conditioned medium of MDA-PCa-2b and E006-A (AA-origin), and PC-3 and Du-145 (CA origin) cell lines. Exo-miRs profiling was performed to study the differential expression of AA vs CA in cells. The potential candidates were validated in Exo procured from plasma of forty AA and CA PCa patients and their aged-matched healthy subjects (n=20) using real-time PCR analysis. Circulating miRs were also determined in the plasma. The sensitivity and specificity of Exo-miRs were assessed using receiver operating characteristic (ROC) curve analysis. Results: Exosomes-associated miR-3613 and miR-3128 were downregulated (P<0.001) in PCa regarding normal subjects. These Exo-miRs were also downregulated (p<0.01) in AA versus CA PCa. Exo-miR-3128 was able to discriminate PCa patients from normal subjects (AUC=0.70) and when age and Gleason score were combined to miR-3128, the discriminatory power was increased (AUC=1.00). Exo-miR-3128 was able to segregate AA from CA PCa (AUC=0.63) and when Exo-miR-3128 combined with -miR-3613, the power was increased (AUC=0.84, P<0.01). Conclusion: Our findings underline the role of exosomes-associated miRs in health disparity of PC. The differential expression of miRs in AA men demonstrates their potential role as prognostic markers in the context of racial disparity. Citation Format: Hamdy Ali, Andrew B. Sholl, Pei-Yau Lung, Juan Bustamante, Jinfeng Zhang, King S. Coffield, Zakaria Y. Abd Elmageed. Exosomes-associated miR-3128 and miR-3613 are dysregulated in African American men with prostate cancer and correlated with poor prognosis [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 B44.