Molina-Pelayo Francisco A, Zarate-Lopez David, García-Carrillo Rosendo, Rodríguez-Beas César, Íñiguez-Palomares Ramón, Rodríguez-Mejía José L, Soto-Guzmán Adriana, Velasco-Loyden Gabriela, Sierra-Martínez Mónica, Virgen-Ortiz Adolfo, Sánchez-Pastor Enrique, Magaña-Vergara Nancy E, Baltiérrez-Hoyos Rafael, Alamilla Javier, Chagoya de Sánchez Victoria, Dagnino-Acosta Adán, Chávez Enrique, Castro-Sánchez Luis
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Colima 28045, Colima, Mexico.
Departamento de Física, Universidad de Sonora, Hermosillo 83000, Sonora, Mexico.
Int J Mol Sci. 2025 Mar 12;26(6):2563. doi: 10.3390/ijms26062563.
Hepatocellular carcinoma (HCC) is the most common primary liver cancer, often diagnosed at advanced stages due to insufficient early screening and monitoring. MicroRNAs (miRNAs) are key regulators of gene expression and potential biomarkers for cancer diagnosis. This study investigated the diagnostic potential of miRNAs in Extracellular Vesicles (EVs) from HCC. miRNA expression in EVs was analyzed using HCC cell lines, circulating EVs from a Diethylnitrosamine (DEN)-induced liver tumor rat model, and plasma samples from HCC patients. Receiver Operating Characteristics (ROCs) were applied to evaluate the diagnostic accuracy of circulating EV miRNAs in patients. Five miRNAs (miR-183-5p, miR-19a-3p, miR-148b-3p, miR-34a-5p, and miR-215-5p) were consistently up-regulated in EVs across in vitro and in vivo HCC models. These miRNAs showed statistically significant differences in HCC patients stratified by TNM staging and Edmondson-Steiner grading compared to healthy controls. They also differentiated HCC patients with various etiologies from the control group and distinguished HCC patients, with or without liver cirrhosis, from cirrhotic and healthy individuals. Individually and as a panel, they demonstrated high sensitivity, specificity, and accuracy in identifying HCC patients. Their consistent upregulation across models and clinical samples highlights their robustness as biomarkers for HCC diagnosis, offering the potential for early disease management and prognosis.
肝细胞癌（HCC）是最常见的原发性肝癌，由于早期筛查和监测不足，往往在晚期才被诊断出来。微小RNA（miRNA）是基因表达的关键调节因子，也是癌症诊断的潜在生物标志物。本研究调查了HCC细胞外囊泡（EV）中miRNA的诊断潜力。使用HCC细胞系、二乙基亚硝胺（DEN）诱导的肝肿瘤大鼠模型的循环EV以及HCC患者的血浆样本分析了EV中的miRNA表达。应用受试者工作特征（ROC）曲线评估循环EV miRNA对患者的诊断准确性。在体外和体内HCC模型中，5种miRNA（miR-183-5p、miR-19a-3p、miR-148b-3p、miR-34a-5p和miR-215-5p）在EV中持续上调。与健康对照相比，这些miRNA在按TNM分期和Edmondson-Steiner分级分层的HCC患者中显示出统计学上的显著差异。它们还能将不同病因的HCC患者与对照组区分开来，并将有或无肝硬化的HCC患者与肝硬化患者和健康个体区分开来。单独或作为一个组合，它们在识别HCC患者方面表现出高灵敏度、特异性和准确性。它们在不同模型和临床样本中的持续上调突出了它们作为HCC诊断生物标志物的稳健性，为早期疾病管理和预后提供了潜力。
