Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men

Hamdy E A Ali; Mohamed S A Gaballah; Rofaida Gaballa; Shahenda Mahgoub; Zeinab A Hassan; Eman A Toraih; Bettina F Drake; Zakaria Y Abd Elmageed

doi:10.3390/cancers13205236

Small Extracellular Vesicle-Derived microRNAs Stratify Prostate Cancer Patients According to Gleason Score, Race and Associate with Survival of African American and Caucasian Men

Cancers (Basel). 2021 Oct 19;13(20):5236. doi: 10.3390/cancers13205236.

Authors

Hamdy E A Ali^{1

2}, Mohamed S A Gaballah^{1

3}, Rofaida Gaballa¹, Shahenda Mahgoub³, Zeinab A Hassan³, Eman A Toraih⁴, Bettina F Drake⁵, Zakaria Y Abd Elmageed^{1

6}

Affiliations

¹ Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University, College Station, TX 77843, USA.
² Department of Radiobiological Applications, Nuclear Research Center, Atomic Energy Authority, Cairo 13759, Egypt.
³ Department of Biochemistry and Molecular Biology, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt.
⁴ Department of Surgery, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
⁵ Division of Public Health Sciences, School of Medicine, Washington University, Saint Louis, MO 63110, USA.
⁶ Department of Pharmacology, Edward Via College of Osteopathic Medicine, University of Louisiana at Monroe, Monroe, LA 71203, USA.

Abstract

The utility of small extracellular vesicles (sEVs)-derived microRNAs (miRs) to segregate prostate cancer (PCa) patients according to tumor aggressiveness and ancestral background has not been fully investigated. Thus, we aimed to determine the diagnostic and prognostic utility of sEV-associated miRs in identifying aggressive PCa in African American (AA) and Caucasian (CA) men. Using a training cohort, miR profiling was performed on sEVs isolated from plasma of PCa patients. Top-ranked sEV-associated miRs were then validated in 150 plasma samples (75 AA and 75 CA) collected from two independent cohorts; NIH (n = 90) and Washington University (n = 60) cohorts. Receiver operating characteristic (ROC) curve, Kaplan-Meier and Cox proportional hazards regression were used to assess these miRs as clinical biomarkers. Among nine top-ranked sEV-associated miRs, miR-6068 and miR-1915-3p were enriched in sEVs collected from PCa patients compared to healthy volunteers. Moreover, miR-6716-5p and miR-3692-3p segregated AA from CA men and low from high Gleason score (GS), respectively. Upregulation of sEV-associated miR-1915-3p, miR-3692-3p and miR-5001-5p was associated with improved survival time, and only miR-1915-3p was associated with longer recurrence-free survival (RFS) as an independent prognostic marker. Taken together, we identified novel sEV-associated miRs that can differentiate PCa patients from normal, AA from CA and high from low GS and predicts RFS.

Keywords: African American; biomarker; clinical outcomes; prostate cancer; small extracellular vesicle-associated microRNAs.

Grants and funding

R21CA194750/National Institutes of Health