胆管癌的蛋白质组学分析  

Proteomic analysis of cholangiocarcinoma

作　　者：吕济相[1] 王济明[1] 罗诗樵[1] 黄国飞[1] 

机构地区：[1]重庆医科大学附属第一医院肝胆外科,重庆400016

出　　处：《中国癌症杂志》2010年第6期411-415,共5页China Oncology

基　　金：重庆市卫生局2007年度医学科研项目计划(07-01-003)

摘　　要：背景与目的:胆管癌是目前常见的消化道恶性肿瘤,早期诊断困难,总体5年生存率极低,所以改善预后的关键在于早期诊断。近年来,蛋白质组学的迅猛发展,为检测肿瘤标志物提供了一种新技术。本研究通过比较胆管癌组织与正常胆管组织的蛋白质组表达差异,寻找胆管癌相关的蛋白质,选择敏感的分子标志物。方法:运用蛋白质组学技术,对16例胆管癌患者的胆管癌组织和正常胆管组织进行胶内差异双向凝胶电泳(2-DE),选择差异表达超过2倍的蛋白质进行MALDI-TOF质谱分析和生物信息学分析。结果:成功建立胆管癌组织和正常组织的双向凝胶电泳图谱,胆管癌组织和正常胆管组织平均蛋白质斑点数分别为1087和1048,其中表达差异超过2倍的斑点共有32个,质谱分析和数据库检索共鉴定出l8种蛋白质,包括衔接蛋白成纤维细胞生长因子受体底物2(fibroblast growth factor recptor substrate2,FRS2)、连环蛋白(catenin,beta1)、细胞外信号调节激酶(extracellular response kinase)等。从功能上分析,这些差异蛋白质与癌细胞的发生、增殖、分化、转移等相关。结论:胆管癌组织与正常胆管组织间有l8种差异蛋白质可能为研究胆管癌的生物学行为提供新的分子标记物。Background and purpose： Cholangiocarcinoma is a common digestive tract cancer which is difficult to be early diagnosed, and has a low overall 5-year survival rate. Early diagnosis plays an important role in improving its prognosis. The proteome develops so rapidly that it has provided a new technology for tumor markers in recent years. This study was aimed to investigate cancer associated proteins and sensitive biomarkers in cholangiocarcinoma. Methods： Two-dimensional gel electrophoresis was used to define patterns of protein expression in cholangiocarcinoma and these patterns were matched to normal tissues from 16 patients. Proteins that showed differential expression of a 2-fold change were cut and analyzed by MALDI-TOF mass spectrometry. Results： Two-dimensional protein maps of cholangiocarcinoma and matched normal tissues were gained successfully. Gelanalysis software identified an average of 1 087 spots in cholangiocarcinoma, while 1 048 were identified in matched normal tissue and statistical filtering yielded 32 spots of a 2-fold change, of which, 18 were identified by using mass spectrometry. These 18 included fibroblast growth factor receptor substrate 2 （FRS2）, catenin, beta 1, extracellular response kinase, etc. Functional analysis revealed that these proteins were associated with cancer cellular oncogenesis, proliferation, differentiation and metastasis. Conclusion： Proteomic analysis could identify proteins with variance in cholangiocarcinoma versus in normal tissues as well as be able to provide probable 18 new biomarkers correlated with biological behavior of cholangiocarcinoma.

关 键 词：胆管癌 蛋白质组学 双向凝胶电泳 

分 类 号：R735.8[医药卫生—肿瘤]