从肝硬化和肝细胞癌患者血浆来源的细胞外囊泡中发现候选生物标志物:一项探索性蛋白质组学研究。
Discovery of candidate biomarkers from plasma-derived extracellular vesicles of patients with cirrhosis and hepatocellular carcinoma: an exploratory proteomic study.
发表日期:2024 Jul 16
作者:
Cecilia Zertuche-Martínez, Juan Manuel Velázquez-Enríquez, Karina González-García, Jovito Cesar Santos-Álvarez, María de Los Ángeles Romero-Tlalolini, Socorro Pina-Canseco, Laura Pérez-Campos Mayoral, Pablo Muriel, Saúl Villa-Treviño, Rafael Baltiérrez-Hoyos, Jaime Arellanes-Robledo, Verónica Rocío Vásquez-Garzón
来源:
Protein & Cell
摘要:
细胞外囊泡(EV)因其生物分子负载而成为一种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) 患者血浆来源的 EV 中鉴定候选蛋白质生物标志物。使用 LC-MS/MS 对来自健康参与者 (HP)、LC 和 HCC 患者(各 8 个样本)的血浆来源的 EV 进行无标记定量蛋白质组分析。共鉴定出248个蛋白,两两比较后获得差异表达蛋白(DEP)。我们发现DEP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癌变过程的上调和下调蛋白,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,可以区分这两种疾病。此外,我们还确定了两种疾病中最常见的共享蛋白,其中包括 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发挥重要作用,并代表了一组用于 LC 和 HCC 预后和诊断的候选生物标志物。
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.