基于iTRAQ多重化学标记串联质谱技术筛选肝细胞癌的生物标记物  

Search for Potential Serum Biomarkers in Hepatocellular Carcinoma Using iTRAQ-Coupled LC-MS/MS

作　　者：刘韬韬[1] 薛如意[1] 黄晓武[2] 吴昊[1] 沈锡中[1] 

机构地区：[1]复旦大学附属中山医院消化科,上海200032 [2]复旦大学附属中山医院肝肿瘤外科,上海200032

出　　处：《中国临床医学》2010年第6期771-774,共4页Chinese Journal of Clinical Medicine

基　　金：国家重点基础研究发展计划(973)(编号:2007CB936000);国家重大科技专项(编号:2009ZX10004-301;2008ZX10002-017);上海人才发展基金(编号:2009-035);国家自然科学基金资助项目(编号:30772505;编号:30872503)

摘　　要：目的:利用同位素标记相对和绝对定量(iTRAQ)技术筛选并鉴定合并乙肝病毒(HBV)感染的肝细胞癌(HCC)患者和慢性乙肝患者的血清差异表达的蛋白质。方法:收集HBV感染的HCC患者血清16例(HCC组),慢性乙肝患者血清13例(慢性乙肝组),组内等量混合后利用高效液相色谱柱去除高丰度蛋白,样本经iTRAQ试剂标记后利用二维色谱分离,经串联质谱鉴定并相对定量。结果:质谱共得到49784个多肽片段,经谱库搜索的鉴定的蛋白共279个,其中差异表达的蛋白有28种,HCC组较慢性乙肝组上调的蛋白有20种,下调的有8种。其中上调的蛋白包括α1-抗胰蛋白酶、α1-酸性糖蛋白1、血清淀粉样蛋白A、C反应蛋白,结合珠蛋白等5个急性相反应蛋白,提示炎性反应和肿瘤间存在一定的联系。结论:筛选出多种与肝癌相关的差异蛋白,提示iTRAQ技术对于血清蛋白质组学肿瘤标记物的研究有很好的应用前景。Objective：To apply the iTRAQ-coupled liquid chromatography and tandem mass spectrometry（LC-MS/MS） technology to identify proteins differentially regulated in serums of HBV-related hepatocellular carcinoma（HCC）.Methods： The study included serum samples from 16 HCC patients with hepatitis B virns（HBV） infection and 13 samples from chronic hepatitis B patients.Proteins differentially regulated in serums of HBV-related HCC were identified by the iTRAQ-coupled LC-MS/MS technology.Results：Collectively,the number of peptide spectra identified was 49784,of which 279 non-redundant proteins were identified.20 proteins were over-expressed and 8 proteins were under-expressed in HCC.Five acute phase proteins（alpha1-antitrypsin,alpha1-acid glycoprotein 1,serum amyloid A protein,C-reactive protein and haptoglobin） were found up-regulated,implying a close linkage between inflammation and malignancy.Conclusions：This pilot study suggests that iTRAQ technology may help us to identify novel serum markers for early diagnosis of HCC.

关 键 词：肝细胞癌 蛋白质组学 血清生物标志物 

分 类 号：R735.7[医药卫生—肿瘤]