Zertuche-Martínez Cecilia, Velázquez-Enríquez Juan Manuel, González-García Karina, Santos-Álvarez Jovito Cesar, Romero-Tlalolini María de Los Ángeles, Pina-Canseco Socorro, Pérez-Campos Mayoral Laura, Muriel Pablo, Villa-Treviño Saúl, Baltiérrez-Hoyos Rafael, Arellanes-Robledo Jaime, Vásquez-Garzón Verónica Rocío
Laboratorio de Fibrosis y cáncer, Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico.
CONAHCYT-Facultad de Medicina y Cirugía, Universidad Autónoma Benito Juárez de Oaxaca, Oaxaca de Juárez 68120, Oaxaca, Mexico.
Mol Omics. 2024 Aug 12;20(7):483-495. doi: 10.1039/d4mo00043a.
Extracellular vesicles (EVs) represent an attractive source of biomarkers due to their biomolecular cargo. The aim of this study was to identify candidate protein biomarkers from plasma-derived EVs of patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Plasma-derived EVs from healthy participants (HP), LC, and HCC patients (eight samples each) were subjected to label-free quantitative proteomic analysis using LC-MS/MS. A total of 248 proteins were identified, and differentially expressed proteins (DEPs) were obtained after pairwise comparison. We found that DEPs mainly involve complement cascade activation, coagulation pathways, cholesterol metabolism, and extracellular matrix components. By choosing a panel of up- and down-regulated proteins involved in cirrhotic and carcinogenesis processes, TGFBI, LGALS3BP, C7, SERPIND1, and APOC3 were found to be relevant for LC patients, while LRG1, TUBA1C, TUBB2B, ACTG1, C9, HP, FGA, FGG, FN1, PLG, APOB and ITIH2 were associated with HCC patients, which could discriminate both diseases. In addition, we identified the top shared proteins in both diseases, which included LCAT, SERPINF2, A2M, CRP, and VWF. Thus, our exploratory proteomic study revealed that these proteins might play an important role in the disease progression and represent a panel of candidate biomarkers for the prognosis and diagnosis of LC and HCC.
细胞外囊泡（EVs）因其生物分子载荷而成为有吸引力的生物标志物来源。本研究的目的是从肝硬化（LC）和肝细胞癌（HCC）患者的血浆来源的细胞外囊泡中鉴定候选蛋白质生物标志物。使用液相色谱-串联质谱（LC-MS/MS）对健康参与者（HP）、LC和HCC患者（每组8个样本）的血浆来源的细胞外囊泡进行无标记定量蛋白质组分析。共鉴定出248种蛋白质，并通过两两比较获得差异表达蛋白质（DEPs）。我们发现DEPs主要涉及补体级联激活、凝血途径、胆固醇代谢和细胞外基质成分。通过选择一组参与肝硬化和致癌过程的上调和下调蛋白质，发现TGFBI、LGALS3BP、C7、SERPIND1和APOC3与LC患者相关，而LRG1、TUBA1C、TUBB2B、ACTG1、C9、HP、FGA、FGG、FN1、PLG、APOB和ITIH2与HCC患者相关，这些蛋白质可以区分这两种疾病。此外，我们还鉴定了两种疾病中共享的顶级蛋白质，包括LCAT、SERPINF2、A2M、CRP和VWF。因此，我们的探索性蛋白质组学研究表明，这些蛋白质可能在疾病进展中起重要作用，并代表一组用于LC和HCC预后和诊断的候选生物标志物。
