早期肝纤维化外周血清标志物筛选的初步研究

Preliminary study of screening potential serum markers for Hepatitis B-related liver fibrosis

目的探讨早期病毒性乙型肝炎(乙肝)肝纤维化的潜在血清标志物并建立相应的诊断模型。方法采用表面增强激光解吸/离子化时间飞行质谱(SELDI-TOF-MS)技术检测20个健康人和31例早期乙肝肝纤维化患者的血清蛋白质谱,用biomarker Wizard软件筛选出早期肝纤维化的差异表达蛋白质谱峰,用Biomarker Pattern软件对差异蛋白峰值进行线性分析并建立诊断模型。结果在分子量为2000～20000Da的区间内检测出97个峰值,15个为差异蛋白峰,其中早期肝纤维化患者有3个上调,12个下调。用质荷比为M4799和M6125的差异蛋白联合建立的诊断模型最优,其特异度为80%(16/20),灵敏度为87%(27/31)。结论 SELDI-TOF-MS在筛选早期肝纤维化血清学标志物方面具有较高的灵敏度和特异性,作为肝纤维化早期筛选的方法尚需大宗病例证实及临床后续验证。

Objective To explore new potential serological biomarkers and develop diagnostic model for mild Hepatitis B related liver fibrosis.Methods 31 patients with mild liver fibrosis and 20 healthy people were recruited,Surface-enhanced laser desorption/ionisation time-of-flight mass spectrometry（SELDI-TOF-MS） was applied to generate the serum protein spectra,furthermore biomarker Wizard software was used to screen differentially expressed protein peaks and to compare the average intensity of the same peaks between the two groups,ultimately data was analyzed and diagnostic model was established by Biomarker Pattern software.Results The test screened 97 peaks between 2000 and 20 000 Da,15 of them were differentially expressed protein peaks,in which 3 were up-regulated and 12 were down-regulated.M4799 and M6125 were considered the best diagnostic model after these two protein peaks were combined together,the Specificity was 80.0%（16/20）and Sensitivity was 87.1%（27/31）.Conclusion SELDI-TOF-MS technology has the advantage of quickness,practicality,high Specificity and high Sensitivity in screening mild liver fibrosis,but Large scale clinical trials and further clinical studies were needed to confirm this technology as a new screening way for hepatitis B-related liver fibrosis.