应用SELDI蛋白芯片技术对肝炎后肝硬化早期癌变的蛋白质组学研究

A serum proteomics study on early cancerization of post-hepatitic cirrhosis by SELDI protein chip technique

目的探讨肝炎后肝硬化早期癌变的血清蛋白质组学特点。方法应用表面增强激光解吸离子化飞行时间质谱仪(SELDI-TOF-MS)结合铜离子蛋白芯片检测62例肝炎后肝硬化与100例Ⅰ-Ⅱ期(T1-2N0M0)肝癌并肝硬化患者的血清蛋白质谱,采用Biomarker Wizard和Biomarker Patterns软件分析并建立分类树模型,并对分类树模型的诊断效能进行验证。结果对肝炎后肝硬化与肝癌并肝硬化患者的血清蛋白质谱进行分析,建立了由4种差异蛋白组成的分类树模型。采用该分类树模型在学习模式下对100例肝癌伴肝硬化、62例肝炎肝硬化患者进行分组,准确率为99.4%(161/162),诊断肝癌伴肝硬化的灵敏度和特异度分别为99.0%(99/100)、100.0%(62/62),在测试模式下对上述患者进行分组,其准确率为94.4%(153/162),诊断肝癌伴肝硬化的灵敏度和特异度分别为95.0%(95/100)、93.5%(58/62)。结论应用SELDI蛋白芯片技术筛选肝炎后肝硬化早期癌变具有方便、快捷、灵敏度高、特异性强的优点。

Objective To explore the serum proteomics characteristics of early carcerization of post-hepatitic cirrhosis.MethodsThe serum protein profiles were detected of 62 patients with post-hepatitic cirrhosis and 100 patients with hepatic carcinoma in Ⅰ-Ⅱ stage （T1-2N0M0） and cirrhosis by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry （SELDI-TOF-MS） IMAC30-Cu2＋ ProteinChip array （Ciphergen Biosystems Inc.,USA）,the distinct proteins were analyzed and a classification tree model was established by using Biomarker Patterns software.The diagnostic efficacy of the model was blindly tested using the serum protein from both groups.ResultsThe serum protein profiles of post-hepatitic cirrhosis and hepatic carcinoma complicating with cirrhosis were analyzed and a classification tree model was established including 4 distinct proteins with different M/Z.In the training mode,the accuracy was 99.4% （161/162） on differential diagnosis to differentiate post-hepatitic cirrhosis and hepatic carcinoma complicating with cirrhosis,the sensitivity and specificity were 99.0% （99/100） and 100.0% （62/62）,respectively,on the diagnosis of hepatic carcinoma complicating with cirrhosis.In the testing mode,the accuracy of differential diagnosis was 94.4% （153/162）,the sensitivity and specificity were 95.0% （95/100） and 93.5% （58/62） on the diagnosis of hepatic carcinoma complicating with cirrhosis.ConclusionSELDI-TOF-MS ProteinChip technique is of convenient and rapid,and with high sensitivity and specificity on the diagnosis of early carcerization of post-hepatitic cirrhosis.