Background: The morbidity and mortality rates of prostate cancer (PCa) in African American (AA) are 2-3 times higher than European American (EuA) men. The molecular mechanisms underlying the aggressiveness of PCa have not fully identified. Thus, our aim was to evaluate the diagnostic/prognostic utility of exosomal microRNAs (miRs) to classify PCa patients according their race and aggressive phenotype in AA patients. Their functional role in tumor aggressiveness was also determined.
Methods: Exosomes were isolated from the conditioned media of AA and EuA PCa cell lines. The expression of miRs was validated in exosomes, free-circulating plasma, and FFPE tissue specimens of forty AA and EuA patients using quantitative real-time PCR analysis. The sensitivity and specificity of exosomal miRs to classify prostate cancer patients according their race and aggressiveness were assessed using receiver operating characteristic (ROC) curve analysis. To study the functional significance of exosomal miRs, cell proliferation, clonogenic, cell cycle and migration assays were performed in PCa cells transfected with miR-3128.
Results: Differential expression of exosomal miR-3613-3p, miR-3218, miR-3679, and miR-3680 was demonstrated in the plasma of AA versus EuA of PCa patients. While exosomal miR-3613 and miR-3679 (p<0.05) were upregulated, free-circulating miRs downregulated (p<0.05) in the plasma of AA versus EuA patients. The accuracy of miR-3679 to discriminate AA from EuA was improved when combined with the other three miRs (AUC jumped from 0.717 to 0.897). Intriguingly, miR-3128 showed a dual role in AA versus EuA cells. Overexpression of miR-3128 increased the cell growth in AA cells while it did the opposite in EuA cells. These data were recapitulated by migration, cell cycle and clonogenic assays.
Conclusion: Our findings underline the role of exosomal miRs in health disparity of PCa. The differential expression of miRs in AA men demonstrates their reliability as biomarkers and their potential role in promoting tumor aggressiveness in
Citation Format: Hamdy E.A. Ali, Rofaida Gaballa, Andrew S. Sholl, Mohamed Gaballah, Juan J. Bustamante, Preeti Zanwar, Hamed I. Ali, Zakaria Y. Abd Elmageed. Exosomal microRNAs are associated with prostate cancer aggressiveness in African American patients [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B045.