Elevating prostate cancer diagnostics through extracellular vesicle miRNAs.

In this edition of Gene's 'Editor's Corner,' we highlight the emerging potential of extracellular vesicle-derived miRNAs as valuable biomarkers for prostate cancer diagnostics. In the recent issue of Gene (Gene 939, 2025, 149186), Nobrega et al. 1 present a compelling study that advances the field of liquid biopsy by comparing extracellular vesicle-incorporated microRNAs (EV-miRNAs) with cell-free microRNAs (cfmiRNAs) as biomarkers for prostate cancer. The authors analyzed four miRNAs-miR-21-5p, miR-200c- 3p, miR-375-3p, and miR-1290-3p-across plasma samples from healthy individuals, patients with localized prostate cancer, and those with metastatic disease. Their findings demonstrate that EV-miRNAs are not only more abundant and stable than cf-miRNAs but also exhibit significantly higher expression in cancer patients. Notably, EV-miR-375-3p and EV-miR-1290-3p emerged as particularly promising, showing strong diagnostic accuracy and clear associations with higher ISUP grades and PSA levels. These results underscore the potential of EV-miRNAs as non-invasive, clinically relevant biomarkers that could enhance current diagnostic tools, especially in cases where PSA levels are inconclusive. This study builds on earlier work, such as the 2017 investigation by Endzeliņš et al. 2 which also compared EV-miRNAs and cf-miRNAs in prostate cancer. While that study found distinct expression profiles between the two forms, it suggested that certain miRNAs, like miR-200c-3p and miR-21-5p, performed better in EVs, whereas miR-375 was more informative in whole plasma. Nobrega et al. extend these findings by demonstrating that all four miRNAs studied perform better when isolated from EVs, with miR-1290-3p showing particularly high diagnostic and prognostic value. The conclusions of this study are further supported by recent literature. A 2024 review in the Journal of Pharmaceutical Investigatio 3 highlights the biological advantages of EVs, particularly their ability to protect and deliver miRNAs with enhanced stability and targeting efficiency. Similarly, the Springer volume Extracellular Vesicle: Biology and Translational Application 4 details the mechanisms of EV biogenesis and cargo selection, reinforcing the notion that EVs offer a more reliable platform for miRNA-based diagnostics.