Ali Hamdy E A, Gaballah Mohamed S A, Gaballa Rofaida, Mahgoub Shahenda, Hassan Zeinab A, Toraih Eman A, Drake Bettina F, Abd Elmageed Zakaria Y
Department of Pharmaceutical Sciences, Rangel College of Pharmacy, Texas A&M University, College Station, TX 77843, USA.
Department of Radiobiological Applications, Nuclear Research Center, Atomic Energy Authority, Cairo 13759, Egypt.
Cancers (Basel). 2021 Oct 19;13(20):5236. doi: 10.3390/cancers13205236.
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 ( = 90) and Washington University ( = 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.
小细胞外囊泡（sEVs）衍生的微小RNA（miRs）根据肿瘤侵袭性和祖先背景对前列腺癌（PCa）患者进行分类的效用尚未得到充分研究。因此，我们旨在确定sEV相关miRs在识别非裔美国（AA）和白种（CA）男性侵袭性PCa中的诊断和预后效用。使用一个训练队列，对从PCa患者血浆中分离的sEV进行miR分析。然后在从两个独立队列收集的150份血浆样本（75份AA和75份CA）中验证排名靠前的sEV相关miRs；国立卫生研究院（=90）和华盛顿大学（=60）队列。采用受试者工作特征（ROC）曲线、Kaplan-Meier和Cox比例风险回归来评估这些miRs作为临床生物标志物。在九个排名靠前的sEV相关miRs中，与健康志愿者相比，miR-6068和miR-1915-3p在从PCa患者收集的sEV中富集。此外，miR-6716-5p和miR-3692-3p分别将AA男性与CA男性以及低Gleason评分（GS）与高Gleason评分区分开来。sEV相关miR-1915-3p、miR-3692-3p和miR-5001-5p的上调与生存时间延长相关，并且只有miR-1915-3p作为独立预后标志物与无复发生存期（RFS）延长相关。综上所述，我们鉴定出了能够区分PCa患者与正常人、AA与CA以及高GS与低GS并预测RFS的新型sEV相关miRs。
