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丙型肝炎病毒血清蛋白质组:寻找纤维化蛋白标志物。

The HCV serum proteome: a search for fibrosis protein markers.

作者信息

Cheung K J, Tilleman K, Deforce D, Colle I, Van Vlierberghe H

机构信息

Department of Hepatology and Gastroenterology, Ghent University Hospital, Ghent, Belgium.

出版信息

J Viral Hepat. 2009 Jun;16(6):418-29. doi: 10.1111/j.1365-2893.2009.01083.x. Epub 2009 Feb 15.

Abstract

Liver fibrosis/cirrhosis is a serious health issue in hepatitis C virus (HCV-) infected patients and is currently diagnosed by the invasive liver biopsy. The aim of this study was to find useful fibrosis markers in HCV-patients' sera of different fibrosis degrees (METAVIR F0-F4) based on proteomics. Serum proteome profiles were created by two-dimensional gel electrophoresis. Profiles were analysed between different degrees of fibrosis (F0-F4) and between early (F0F1) and late (F2F3F4) fibrosis by univariate analyses (P <or= 0.05). Differentially expressed proteins were subsequently identified by mass spectrometry. Mac-2-binding protein, alpha-2-macroglobulin and hemopexin were increased in F4 opposite F0/F1. A-1-antitrypsin, leucine-rich alpha-2-glycoprotein and fetuin-A were decreased in F4 opposite F0/F1. Late fibrosis was characterized by an increase in Mac-2-binding protein, alpha-2-macroglobulin and alpha-1B-glycoprotein expression and a decrease in haptoglobin expression. Mac-2-binding protein expression was confirmed by dot blot assay and enzyme-linked immunosorbent assay in a secondary population. In conclusion, serum proteome analysis enabled the detection/identification of existing and new candidate markers in line with fibrosis progression in HCV-patients.

摘要

肝纤维化/肝硬化是丙型肝炎病毒(HCV)感染患者面临的一个严重健康问题,目前通过侵入性肝活检进行诊断。本研究的目的是基于蛋白质组学在不同纤维化程度(METAVIR F0 - F4)的HCV患者血清中寻找有用的纤维化标志物。通过二维凝胶电泳创建血清蛋白质组图谱。通过单变量分析(P≤0.05)分析不同纤维化程度(F0 - F4)之间以及早期(F0F1)和晚期(F2F3F4)纤维化之间的图谱。随后通过质谱鉴定差异表达的蛋白质。与F0/F1相比,F4中Mac - 2结合蛋白、α - 2巨球蛋白和血红素结合蛋白增加。与F0/F1相比,F4中α - 1抗胰蛋白酶、富含亮氨酸的α - 2糖蛋白和胎球蛋白A减少。晚期纤维化的特征是Mac - 2结合蛋白、α - 2巨球蛋白和α - 1B糖蛋白表达增加,触珠蛋白表达减少。在另一组人群中通过斑点印迹分析和酶联免疫吸附测定证实了Mac - 2结合蛋白的表达。总之,血清蛋白质组分析能够检测/鉴定与HCV患者纤维化进展一致的现有和新的候选标志物。

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