Nobrega Monyse, Reis Mariana Bisarro Dos, Souza Marilesia Ferreira de, Furini Hector Hugo, Costa Brandão Berti Fernanda, Souza Ingrid Larissa Melo, Mingorance Carvalho Tamyres, Zanata Silvio M, Fuganti Paulo Emilio, Malheiros Danielle, Ribeiro Enilze Maria de Souza Fonseca, Cólus Ilce Mara de Syllos
Department of General Biology, State University of Londrina, Londrina, Paraná, Brazil.
Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, São Paulo, Brazil.
Gene. 2025 Mar 5;939:149186. doi: 10.1016/j.gene.2024.149186. Epub 2024 Dec 19.
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.
微小RNA（miRNA）可在细胞内整合到细胞外囊泡中（即细胞外囊泡miRNA，EV-miRNA），也可在细胞外以游离miRNA（cf-miRNA）的形式存在。本研究旨在比较4种在前列腺癌中具有公认作用的miRNA作为cf-miRNA和EV-miRNA的诊断及预后潜力，这些miRNA取自液体活检（LB）。从15名对照（CTR）和30名患者（20名局限性前列腺癌（PCa）患者、10名转移性前列腺癌（mPCa）患者）的全血和血浆细胞外囊泡中分离总RNA。通过逆转录定量聚合酶链反应（RT-qPCR）对miRNA进行定量，并比较三组之间这些miRNA的相对表达情况，同时评估它们与临床病理参数的相关性。绘制受试者工作特征（ROC）曲线以评估miRNA区分不同组别的诊断潜力。总体而言，与cf-miRNA相比，EV-miRNA表达更高。所有分析的EV-miRNA均显示出诊断潜力，曲线下面积（AUC）均高于0.744。与CTR相比，EV-miR-21-5p、EV-miR-375-3p和EV-miR-1290-3p在PCa和mPCa中过表达，而与CTR相比，EV-miR-200c-3p仅在mPCa中过表达。值得注意的是，EV-miR-375-3p和EV-miR-1290-3p能够区分国际泌尿病理学会（ISUP）≥3级的mPCa，显示出它们的预后潜力。此外，EV-miR-1290-3p和EV-4-miR-panel可检测出前列腺特异性抗原（PSA）>10 ng/mL的患者。cf-miRNA的表现低于EV-miRNA，这可以通过EV-miRNA更高的稳定性和特异性来解释，使其优于cf-miRNA。结果表明，液体活检作为一种非侵入性策略，在临床上可行地将EV-miRNA鉴定为PCa的生物标志物，并可能为评估PCa风险分层提供额外信息。
