Serum biomarkers of hepatitis B virus infected liver inflammation: A proteomic study
Serum biomarkers of hepatitis B virus infected liver inflammation: A proteomic study
复制标题
DOI：
10.1002/pmic.200300394
复制
发表时间：
2003-05-01
期刊：
影响因子：
3.4
通讯作者：
Chiu, JF
中科院分区：
文献类型：
--
作者：
He, QY;Lau, GKK;Chiu, JF
B型肝炎病毒（HBV）是一种严重的传染性和广泛的人类病原体，代表了世界范围内的主要健康问题。慢性HBV感染有很高的风险演变成肝细胞癌。虽然在过去的几年中取得了相当大的进展，HBV感染的发病机制仍然是难以捉摸的，明确诊断HBV感染的肝脏信息仍然依赖于活检组织学检查。在本报告中，我们使用蛋白质组学技术对HBV感染的血清样本进行了全面检测，旨在寻找可用作诊断的血清学生物标志物和/或致病性研究的靶蛋白的疾病相关蛋白。通过与正常人和HBV阴性血清样品比较，我们发现HBV感染血清中至少有七种蛋白质发生了显著变化。这些显著改变的蛋白质被鉴定为触珠蛋白β和α 2链、载脂蛋白A-I和A-IV、α 1-抗胰蛋白酶、甲状腺素运载蛋白和DNA拓扑异构酶II β。这些蛋白质的改变不仅表现在数量上，而且表现在模式（或特异性）上，这可能与坏死性炎症评分相关。特别是载脂蛋白A-1在表达水平上呈现异质性变化，具有不同的亚型，α 1-抗胰蛋白酶产生明显不同的片段，这意味着不同的切割途径。这些独特的现象似乎是HBV感染特有的。同时考虑这些蛋白质的数量和亚型的组合可能是用于HBV诊断和治疗的有用的血清生物标志物（或指标）。
Hepatitis B virus (HBV), a serious infectious and widespread human pathogen, represents a major health problem worldwide. Chronic HBV infection has a very high risk of evolving into hepatocellular carcinoma. Although considerable progress was made during the recent past, the pathogenesis of HBV infection is still elusive and a definite diagnosis of HBV infected liver information still relies on biopsy histological test. In this report, we used proteomics technology to globally examine HBV infected serum samples aiming at searching for disease-associated proteins that can be used as serological biomarkers for diagnosis and/or target proteins for pathogenetic study. By comparing with normal and HBV negative serum samples, we found that at least seven proteins were significantly changed in HBV infected sera. These greatly altered proteins were identified to be haptoglobin beta and alpha2 chain, apolipoprotein A-I and A-IV, alpha1-antitrypsin, transthyretin and DNA topoisomerase IIbeta. The alteration of these proteins is displayed not only in quantity but also in patterns (or specificity), which can be correlated with necroinflammatory scores. In particular, apolipoprotein A-1 presents heterogeneous change in expression level with different isoforms and alpha1-antitrypsin produces evidently different fragments implying diverse cleavage pathways. These unique phenomena appear specific to HBV infection. A combination simultaneously considering the quantities and isoforms of these proteins could be a useful serum biomarker (or index) for HBV diagnosis and therapy.