异常糖基化修饰在胆管癌中的病理意义及其早期诊断价值研究

项目名称： 异常糖基化修饰在胆管癌中的病理意义及其早期诊断价值研究

项目编号： No.81201697

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1

项目作者： 赵云鹏

作者单位： 中国人民解放军第二军医大学

项目金额： 23万元

中文摘要： 胆管癌是一种来源于肝内或肝外胆管上皮的恶性肿瘤，最新糖组学研究表明异常糖基化修饰在恶性肿瘤发生发展中具有重要病理意义，而异常糖基化修饰在胆管癌中的研究鲜有报道。本项目在前期疾病糖组学研究基础上，采用高通量荧光糖电泳（DSA-FACE）技术，分析胆管癌外周血清N-糖组图谱特征性改变，在比较并联合现有胆管癌血清标志物的基础上，构建高特异性和灵敏度的胆管癌早诊模型，将现有早诊率提高5-10%；采用western-blot、lectin blot和RT-PCR等方法从不同层面进一步分析胆管癌组织中糖基化程度及相应糖基转移酶表达水平，明确与胆管癌发生发展关系密切的糖基转移酶；针对关键糖基转移酶构建表达/干扰重组体，在细胞学水平研究异常糖基化修饰对癌细胞生物学行为的影响，寻求潜在的阻断胆管癌发生发展的干预靶点。通过本项目的实施，以期在胆管癌早期诊断、发病机制与干预治疗等多环节形成全新突破。

中文关键词： 胆管癌；异常糖基化；GNT-V；诊断模型；

英文摘要： Cholangiocarcinoma(CC) is a malignant tumor derived from intrahepatic or extrahepatic bile duct epithelium cell. The latest studies on glycomics show that abnormal glycosylation plays an important part in the development and progression of carcinogenesis. It is not yet clear that what and how glycosylated modifications occur in CC. Based on our previous N-glycomics researches, the study analyzes N-glycan profilings of sera of CC using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE). Early diagnostic model were constructed with logistic step-wise regression and receiver operating characteristic curve analysis so as to improve the diagnostic performance rate (5-10%) compared to the available tumor markers of CC; The degree of abnormal glycosylation and the expression of corresponding glycosyltransferases were analyzed in CC tissues by western-blot、lectin blot and RT-PCR to clarify the relationship between glycosyltransferase and the progress of CC. The effect of the biological behavior of CC cell lines was investigated upon knock down or knock up the key molecules revealed in tissue study. The study is anticipated to develop a new breakthrough in early diagnosis, pathogenesis and potential target intervention in CC.

英文关键词： :cholangiocarcinoma；abnormal glycosylation；N--acetylglucosaminyltransferase V；diagnostic model；