胆管癌胆汁中肿瘤相关分泌蛋白的筛选与功能分析

项目名称： 胆管癌胆汁中肿瘤相关分泌蛋白的筛选与功能分析

项目编号： No.81201892

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 陈波

作者单位： 厦门大学

项目金额： 23万元

中文摘要： 胆管癌早期诊断标志物的筛选问题一直是困扰临床、亟待解决的科学难题。胆汁是胆管癌细胞生长的局部微环境，肿瘤细胞在发生、发展的过程中会不断地将一些肿瘤相关分泌蛋白排泄到胆汁中，这些蛋白不仅完成了细胞内翻译后修饰的过程，而且其成分也远比组织及血清简单，故低丰度、低分子量的肿瘤标志蛋白在胆汁中更容易被筛选到。我们前期的研究也发现，胆管癌胆汁中存在以hemopexin precursor等为代表的差异表达分泌蛋白，而其与肿瘤增殖、耐药、侵袭、转移等生物学行为的关系以及是否具备潜在早诊价值还有待进一步研究。本课题拟采用2D-DIGE、SILAC等定量蛋白质组学分析方法，以ERCP微创获取的胆管癌胆汁及胆管癌细胞培养物上清为主要研究对象，通过体内外研究相对照的方式筛选并鉴定肿瘤相关分泌蛋白，在后续确证研究与功能分析的基础上进一步探讨其与胆管癌恶性生物学行为的关系，为筛选胆管癌早期诊断标志物提供新的途径。

中文关键词： 胆管癌；胆汁；分泌蛋白质组；肿瘤标志物；

英文摘要： The early detection of cholangiocarcinoma is not easy to practice till today due to lacking of ideal early detection biomarkers. Bile is stored, concentrated and transported in the biliary system after being secreting from the hepatica and the biliary epithelial cell, so abundant bioinformation which relates to the tumorigenesis of biliary tract could be detected from it. In the prior research, we have identified several differential expressed secretory proteins such as hemopexin precursor from bile of chlolangiccarcinoma, but their biological functions related to tumor behavior such as proliferation, chemotherapy resistance, infiltration and invasion have not been established. In addition, its diagnosis significance for cholangiocarcinoma need further study to valuate. In this study, 2D-DIGE and SILAC analysis will be employed to identify differential expressed tumor-associated secretory proteins of cholangiocarcinoma via bile and CM. After that, ELISA，RIA，western-blot, immunohistochemistry and nude mouse model will be adopt to validat the differential expressed tumor-associated secretory proteins in cholangiocarcinoma. By means of these in vivo and in vitro studies, we can not only get a better understanding of tumorigenesis of cholangiocarcinoma, and can get a clue about early detection biomarkers of cholan

英文关键词： Cholangiocarcinoma；bile；secretome；biomarker；