Julio Marianna Kruithof-de
Department for BioMedical Research, Urology Research Laboratory, University of Bern, Bern, Switzerland; Translational Organoid Models, Department for BioMedical Research, University of Bern, Bern, Switzerland; Department of Urology, Inselspital, Bern University Hospital, Bern, Switzerland.
Gene. 2025 Sep 15;965:149662. doi: 10.1016/j.gene.2025.149662. Epub 2025 Jul 9.
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.
在本期《基因》杂志的“编辑视角”中，我们重点介绍了细胞外囊泡衍生的微小RNA作为前列腺癌诊断中有价值的生物标志物的新兴潜力。在最近一期的《基因》杂志（《基因》939卷，2025年，第149186页）中，诺布雷加等人发表了一项引人注目的研究，该研究通过比较细胞外囊泡包裹的微小RNA（EV - miRNAs）和游离微小RNA（cf - miRNAs）作为前列腺癌生物标志物，推动了液体活检领域的发展。作者分析了来自健康个体、局限性前列腺癌患者和转移性疾病患者血浆样本中的四种微小RNA——miR - 21 - 5p、miR - 200c - 3p、miR - 375 - 3p和miR - 1290 - 3p。他们的研究结果表明，EV - miRNAs不仅比cf - miRNAs更丰富、更稳定，而且在癌症患者中表达显著更高。值得注意的是，EV - miR - 375 - 3p和EV - miR - 1290 - 3p表现出特别有前景的特征，显示出很强的诊断准确性，并与更高的国际泌尿病理学会（ISUP）分级和前列腺特异性抗原（PSA）水平有明确关联。这些结果强调了EV - miRNAs作为非侵入性、临床相关生物标志物的潜力，它们可以增强现有的诊断工具，特别是在PSA水平不确定的情况下。这项研究建立在早期工作的基础上，比如2017年恩泽利尼斯等人的调查，该调查也比较了前列腺癌中EV - miRNAs和cf - miRNAs。虽然该研究发现这两种形式之间有不同的表达谱，但表明某些微小RNA，如miR - 200c - 3p和miR - 21 - 5p，在细胞外囊泡中表现更好，而miR - 375在全血浆中信息更丰富。诺布雷加等人扩展了这些发现，证明从细胞外囊泡中分离出的所有四种研究的微小RNA表现更好，其中miR - 1290 - 3p显示出特别高的诊断和预后价值。这项研究的结论得到了近期文献的进一步支持。2024年发表在《药物研究杂志》上的一篇综述强调了细胞外囊泡的生物学优势，特别是它们保护和递送微小RNA的能力，具有更高的稳定性和靶向效率。同样，施普林格出版社的《细胞外囊泡：生物学与转化应用》详细阐述了细胞外囊泡生物发生和货物选择的机制，强化了细胞外囊泡为基于微小RNA的诊断提供更可靠平台的观点。
