Discovery of candidate biomarkers from plasma-derived extracellular vesicles of patients with cirrhosis and hepatocellular carcinoma: an exploratory proteomic study†

IF 3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular omics Pub Date : 2024-07-16 DOI:10.1039/D4MO00043A

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 and Verónica Rocío Vásquez-Garzón

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Abstract

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.

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从肝硬化和肝细胞癌患者的血浆源性细胞外囊泡中发现候选生物标记物：一项探索性蛋白质组学研究。

细胞外囊泡（EVs）因其所携带的生物分子而成为具有吸引力的生物标记物来源。本研究旨在从肝硬化（LC）和肝细胞癌（HCC）患者的血浆衍生EVs中鉴定候选蛋白质生物标记物。研究人员使用 LC-MS/MS 对健康参与者（HP）、肝硬化患者和肝细胞癌患者（各八份样本）的血浆衍生 EVs 进行了无标记定量蛋白质组学分析。共鉴定出 248 种蛋白质，并通过配对比较获得了差异表达蛋白质（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。通过选择涉及肝硬化和癌变过程的上调和下调蛋白，我们发现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，这两种蛋白可以区分这两种疾病。此外，我们还发现了这两种疾病的共有蛋白，包括 LCAT、SERPINF2、A2M、CRP 和 VWF。因此，我们的探索性蛋白质组学研究揭示了这些蛋白质可能在疾病进展中扮演重要角色，并代表了一组用于 LC 和 HCC 预后和诊断的候选生物标志物。

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来源期刊

Molecular omics Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

5.40

自引率

3.40%

发文量

期刊介绍： Molecular Omics publishes high-quality research from across the -omics sciences. Topics include, but are not limited to: -omics studies to gain mechanistic insight into biological processes – for example, determining the mode of action of a drug or the basis of a particular phenotype, such as drought tolerance -omics studies for clinical applications with validation, such as finding biomarkers for diagnostics or potential new drug targets -omics studies looking at the sub-cellular make-up of cells – for example, the subcellular localisation of certain proteins or post-translational modifications or new imaging techniques -studies presenting new methods and tools to support omics studies, including new spectroscopic/chromatographic techniques, chip-based/array technologies and new classification/data analysis techniques. New methods should be proven and demonstrate an advance in the field. Molecular Omics only accepts articles of high importance and interest that provide significant new insight into important chemical or biological problems. This could be fundamental research that significantly increases understanding or research that demonstrates clear functional benefits. Papers reporting new results that could be routinely predicted, do not show a significant improvement over known research, or are of interest only to the specialist in the area are not suitable for publication in Molecular Omics.