Comparative analysis of extracellular vesicles miRNAs (EV-miRNAs) and cell-free microRNAs (cf-miRNAs) reveals that EV-miRNAs are more promising as diagnostic and prognostic biomarkers for prostate cancer

MicroRNAs can be found intracellularly incorporated into extracellular vesicles (EV-miRNAs) or extracellularly as cell-free miRNAs (cf-miRNAs). This study aimed to compare the diagnostic and prognostic potential of four miRNAs with recognized roles in prostate cancer as cf-miRNAs and EV-miRNAs, obtained from liquid biopsies (LB). Total RNA was isolated from whole plasma and plasma EVs from 15 controls (CTR) and 30 patients (20 with localized prostate cancer (PCa), 10 with metastatic prostate cancer (mPCa)). The miRNAs were quantified by RT-qPCR and the relative expression of these miRNAs was compared between the three groups, and their associations with clinicopathological parameters were assessed. Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic potential of the miRNAs in discriminating different groups. Overall, EV-miRNAs showed higher expression compared to cf-miRNAs. All EV-miRNAs analyzed showed diagnostic potential with an area under the curve (AUC) above 0.744. EV-miR-21-5p, EV-miR-375-3p, and EV-miR-1290-3p were overexpressed in PCa and mPCa compared to CTR, while EV-miR-200c-3p was overexpressed only in mPCa in comparison to CTR. Remarkably, EV-miR-375-3p and EV-miR-1290-3p could differentiate mPCa with ISUP >= 3, demonstrating their prognostic potential. In addition, EV-miR-1290-3p and EV-4-miR-panel detected patients with PSA > 10 ng/mL. Cf-miRNAs performed lower than EV-miRNAs, which can be explained by the greater stability and specificity of EV-miRNAs, making them superior to cf-miRNA. The results show that LB, a non-invasive strategy, is clinically feasible to identify EV-miRNAs as biomarkers for PCa and may provide additional information for assessing PCa risk stratification.