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首页> 外文期刊>Journal of Translational Medicine >Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection
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Serum proteomic analysis focused on fibrosis in patients with hepatitis C virus infection

机译：丙型肝炎病毒感染患者的血清蛋白质组学分析

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Background Despite its widespread use to assess fibrosis, liver biopsy has several important drawbacks, including that is it semi-quantitative, invasive, and limited by sampling and observer variability. Non-invasive serum biomarkers may more accurately reflect the fibrogenetic process. To identify potential biomarkers of fibrosis, we compared serum protein expression profiles in patients with chronic hepatitis C (CHC) virus infection and fibrosis. Methods Twenty-one patients with no or mild fibrosis (METAVIR stage F0, F1) and 23 with advanced fibrosis (F3, F4) were retrospectively identified from a pedigreed database of 1600 CHC patients. All samples were carefully phenotyped and matched for age, gender, race, body mass index, genotype, duration of infection, alcohol use, and viral load. Expression profiling was performed in a blinded fashion using a 2D polyacrylamide gel electrophoresis/LC-MS/MS platform. Partial least squares discriminant analysis and likelihood ratio statistics were used to rank individual differences in protein expression between the 2 groups. Results Seven individual protein spots were identified as either significantly increased (α2-macroglobulin, haptoglobin, albumin) or decreased (complement C-4, serum retinol binding protein, apolipoprotein A-1, and two isoforms of apolipoprotein A-IV) with advanced fibrosis. Three individual proteins, haptoglobin, apolipoprotein A-1, and α2-macroglobulin, are included in existing non-invasive serum marker panels. Conclusion Biomarkers identified through expression profiling may facilitate the development of more accurate marker algorithms to better quantitate hepatic fibrosis and monitor disease progression.
机译：背景技术尽管肝活检广泛用于评估纤维化，但仍具有一些重要的缺点，包括半定量，侵入性和受采样和观察者变异性的限制。非侵入性血清生物标志物可能更准确地反映纤维形成过程。为了确定纤维化的潜在生物标志物，我们比较了慢性丙型肝炎（CHC）病毒感染和纤维化患者的血清蛋白表达谱。方法回顾性分析了1600名CHC患者的纯血统数据库，确定了21例无或轻度纤维化的患者（METAVIR分期F0，F1）和23例晚期纤维化（F3，F4）。所有样本均经过仔细的表型分析，并根据年龄，性别，种族，体重指数，基因型，感染持续时间，饮酒和病毒载量进行匹配。使用2D聚丙烯酰胺凝胶电泳/ LC-MS / MS平台以盲法进行表达谱分析。使用偏最小二乘判别分析和似然比统计量对两组之间蛋白质表达的个体差异进行排名。结果鉴定出七个单独的蛋白斑点，其显着升高（α 2 -巨球蛋白，触珠蛋白，白蛋白）或降低（补体C-4，血清视黄醇结合蛋白，载脂蛋白A-1和两种亚型）载脂蛋白A-IV）伴晚期纤维化。现有的非侵入性血清标记物组中包括三种蛋白：触珠蛋白，载脂蛋白A-1和α 2 -巨球蛋白。结论通过表达谱分析鉴定的生物标志物可能有助于开发更精确的标志物算法，以更好地量化肝纤维化并监测疾病进展。

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