BACKGROUND Hepatitis B virus (HBV) is a global health problem, and infected patients if left untreated may develop cirrhosis and eventually hepatocellular carcinoma. This study aims to enlighten pathways associated with HBV related liver fibrosis for delineation of potential new therapeutic targets and biomarkers. METHODS Tissue samples from 47 HBV infected patients with different fibrotic stages (F1 to F6) were enrolled for 2D-DIGE proteomic screening. Differentially expressed proteins were identified by mass spectrometry and verified by western blotting. Functional proteomic associations were analyzed by EnrichNet application. RESULTS Fibrotic stage variations were observed for apolipoprotein A1 (APOA1), pyruvate kinase PKM (KPYM), glyceraldehyde 3-phospahate dehydrogenase (GAPDH), glutamate dehydrogenase (DHE3), aldehyde dehydrogenase (ALDH2), alcohol dehydrogenase (ALDH1A1), transferrin (TRFE), peroxiredoxin 3 (PRDX3), phenazine biosynthesis-like domain-containing protein (PBLD), immuglobulin kappa chain C region (IGKC), annexin A4 (ANXA4), keratin 5 (KRT5). Enrichment analysis with Reactome and Kegg databases highlighted the possible involvement of platelet release, glycolysis and HDL mediated lipid transport pathways. Moreover, string analysis revealed that HIF-1α (Hypoxia-inducible factor 1-alpha), one of the interacting partners of HBx (Hepatitis B X protein), may play a role in the altered glycolytic response and oxidative stress observed in liver fibrosis. CONCLUSIONS To our knowledge, this is the first protomic research that studies HBV infected fibrotic human liver tissues to investigate alterations in protein levels and affected pathways among different fibrotic stages. Observed changes in the glycolytic pathway caused by HBx presence and therefore its interactions with HIF-1α can be a target pathway for novel therapeutic purposes.

中文翻译：

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HBV感染的具有不同纤维化阶段的肝活检的蛋白质组学分析。

背景技术乙型肝炎病毒（HBV）是一个全球性的健康问题，如果不及时治疗，被感染的患者可能会发展为肝硬化，最终发展为肝细胞癌。这项研究旨在阐明与HBV相关的肝纤维化相关的途径，以描述潜在的新治疗靶标和生物标记物。方法选取47例不同纤维化分期（F1至F6）的HBV感染患者的组织样本进行2D-DIGE蛋白质组学筛查。通过质谱鉴定差异表达的蛋白质，并通过蛋白质印迹验证。通过EnrichNet应用程序分析了功能蛋白质组学关联。结果观察到了载脂蛋白A1（APOA1），丙酮酸激酶PKM（KPYM），3-磷酸甘油醛磷酸脱氢酶（GAPDH），谷氨酸脱氢酶（DHE3），醛脱氢酶（ALDH2）的纤维化阶段变化。醇脱氢酶（ALDH1A1），转铁蛋白（TRFE），过氧化物酶3（PRDX3），吩嗪生物合成样结构域蛋白（PBLD），免疫球蛋白K链C区（IGKC），膜联蛋白A4（ANXA4），角蛋白5（KRT5）。使用Reactome和Kegg数据库进行的富集分析强调了血小板释放，糖酵解和HDL介导的脂质转运途径的可能参与。此外，弦分析表明，HIF-1α（缺氧诱导因子1-α）是HBx（乙型肝炎蛋白）的相互作用伴侣之一，可能在肝纤维化中观察到的糖酵解反应和氧化应激改变中起作用。结论据我们所知，这是第一项研究HBV感染的纤维化人肝组织的蛋白质组学研究，以研究蛋白质水平的变化和不同纤维化阶段之间受影响的途径。