Peroxiredoxin 2: a potential biomarker for early diagnosis of hepatitis B virus related liver fibrosis identified by proteomic analysis of the plasma.
Peroxiredoxin 2: a potential biomarker for early diagnosis of hepatitis B virus related liver fibrosis identified by proteomic analysis of the plasma.
复制标题
过氧化还原蛋白 2：通过血浆蛋白质组学分析鉴定的乙型肝炎病毒相关肝纤维化早期诊断的潜在生物标志物
DOI：
10.1186/1471-230x-10-115
复制
发表时间：
2010-10-13
影响因子：
2.4
通讯作者：
He F
中科院分区：
文献类型：
--
作者：
Lu Y;Liu J;Lin C;Wang H;Jiang Y;Wang J;Yang P;He F
肝纤维化是慢性B型肝炎病毒（HBV）感染过程中的一个中期阶段，如不早期治疗，可发展为肝硬化，最终发展为肝细胞癌（HCC）。考虑到肝活检的局限性和患者不愿接受肝活检，需要一种可靠的、无创的诊断系统来预测和评估肝纤维化的治疗和预后。本研究的目的是寻找早期诊断HBV相关肝纤维化的生物标志物。方法选取7例健康志愿者和27例HBV感染者的血浆标本，进行2-DIGE蛋白质组学筛选。使用单因素ANOVA分析来评估所有组之间蛋白质表达的差异。通过蛋白质印迹进一步证实了这种改变。结果随着纤维化进展，纤维蛋白原、胶原、巨球蛋白、血红素结合蛋白、抗胰蛋白酶、前白蛋白、硫氧还蛋白过氧化物酶等蛋白质表达上调。下调的蛋白质包括结合珠蛋白、血清转铁蛋白、CD 5抗原样蛋白、聚集蛋白、载脂蛋白和富含亮氨酸的α 2-糖蛋白。对于轻度纤维化的区分，Prx II的曲线下面积最高。从25个变量中选择4个变量（PT、Pre、HA和Prx II）构建决策树。在训练组中，正常对照组、轻度肝纤维化组、重度肝纤维化组和早期肝硬化组的预测正确率分别为100%、88.9%、95.2%和100%，总的预测正确率为95.9%。Prx Ⅱ的显著上调表达可用于HBV相关性肝纤维化的早期诊断。
BackgroundLiver fibrosis is a middle stage in the course of chronic Hepatitis B virus (HBV) infection, which will develop into cirrhosis and eventually hepatocellular carcinoma (HCC) if not treated at the early stage. Considering the limitations and patients' reluctance to undergo liver biopsy, a reliable, noninvasive diagnostic system to predict and assess treatment and prognosis of liver fibrosis is needed. The aim of this study was to identify biomarkers for early diagnosis of HBV related liver fibrosis.MethodPlasma samples from 7 healthy volunteers and 27 HBV infected patients with different stages of fibrosis were selected for 2-DIGE proteomic screening. One-way ANOVA analysis was used to assess differences in protein expression among all groups. The alteration was further confirmed by western blotting. Plasma levels of 25 serological variables in 42 healthy volunteers and 68 patients were measured to establish a decision tree for the detection of various stages fibrosis.ResultThe up-regulated proteins along with fibrosis progress included fibrinogen, collagen, macroglobulin, hemopexin, antitrypsin, prealbumin and thioredoxin peroxidase. The down-regulated proteins included haptoglobin, serotransferrin, CD5 antigen like protein, clusterin, apolipoprotein and leucine-rich alpha-2-glycoprotein. For the discrimination of milder stage fibrosis, the area under curve for Prx II was the highest. Four variables (PT, Pre, HA and Prx II) were selected from the 25 variables to construct the decision tree. In a training group, the correct prediction percentage for normal control, milder fibrosis, significant fibrosis and early cirrhosis was 100%, 88.9%, 95.2% and 100%, respectively, with an overall correct percent of 95.9%.ConclusionThis study showed that 2-D DIGE-based proteomic analysis of the plasma was helpful in screening for new plasma biomarkers for liver disease. The significant up-expression of Prx II could be used in the early diagnosis of HBV related liver fibrosis.