应用蛋白组学技术筛选肝外胆管癌胆汁肿瘤标志物的初步研究  

A preliminary study of screening bile tumor markers for extrahepatic cholangiocarcinoma with proteomics technology

作　　者：杨建锋[1] 金杭斌[1] 谢璐[1] 顾伟刚[1] 沈红璋 张筱凤[1] Yang Jianfeng fin Hangbin Xie Lu Gu Weigang Shen Hoagzhang Zhang Xiaofeng.(Department of Gastroenterology, The First People＇s Hospital of Hangzhou, Hangzhou 310006, China)

机构地区：[1]杭州市第一人民医院消化内科,310006

出　　处：《中华消化内镜杂志》2016年第11期784-787,共4页Chinese Journal of Digestive Endoscopy

基　　金：浙江省医药卫生科技计划项目（2013KYB204）

摘　　要：目的应用蛋白组学技术检测肝外胆管癌（EHCC）患者胆汁中的差异表达蛋白，筛选可能用于诊断胆管癌的肿瘤标志物。方法收集16例EHCC患者和16例Oddi括约肌功能障碍（SOD）患者胆汁标本，采用同位素相对标记与绝对定量技术（iTRAQ技术）进行蛋白组学分析，对差异表达的蛋白质行质谱鉴定，通过蛋白数据库检索其功能。结果iTRAQ技术成功建立EHCC和SOD患者的胆汁蛋白质图谱，两组分别检测出275和218个蛋白，筛选出表达差异超过2倍的蛋白质共12个，通过数据库确定4种有诊断意义的蛋白质，分别为MUC3a、AnnexinA3、REG3A、Tumor-asso—ciated trypsin inhibitor（TATI），从功能上分析，这些差异蛋白质与癌细胞的发生、增殖、分化、转移等均具有密切的关系。结论iTRAQ技术能很好地检测出胆管癌患者胆汁中的差异表达蛋白，从中筛选出4种潜在的可作为EHCC胆汁肿瘤标志物的蛋白质，可为研究胆管癌的生物学行为提供新的分子标志物。Objective To analyze differentially expressed proteins in bile of extrahepatic cholangio- carcinoma （EHCC） by proteomics technology, and to detect the potential tumor markers for diagnosis of bile duct malignancy. Methods Bile samples from 16 patients with EHCC and 16 patients with sphincter of oddi dysfunction （control） were collected for proteomic analysis by isobaric tags for relative and absolute quantita- tion （iTRAQ）. The differentially expressed proteins were identified by mass spectrometry and retrieved by protein database. Results Protein maps of both EHCC group and control group were established successfully by iTRAQ. Analysis software identified an average of 275 proteins in EHCC group and 218 proteins in control group. Statistical filter screened 12 proteins of more than double difference, 4 of which were of diagnostic value, identified by mass spectrometry, which were MUC3a, Annexin A3, REG3A and Tumor-associated trypsin inhibitor （TATI）. Functional analysis revealed that these proteins were associated with cancer cellular oncogenesis, proliferation, differentiation and metastasis. Conclusion Proteomic analysis by iTRAQ can i- dentify the protein variance in bile of patients with EHCC, and identify four new potential biomarkers correla- ted with biological behavior of cholangiocarcinoma.

关 键 词：胆管上皮癌 胆管 肝外 蛋白组学 胆汁 肿瘤标记 

分 类 号：R735.8[医药卫生—肿瘤]