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目的:探讨胆管细胞癌组织酪氨酸磷酸化信号通路变化及相关分子情况,以寻找新的治疗靶点。方法:免疫亲和、LC-MS/MS分析识辨胆管癌病人(n=23)750多种不同蛋白质中1 000多个酪氨酸磷酸化位点。结果:胆管细胞癌在DDR1、EPHA2、EGFR和ROS1表现最高水平酪氨酸激酶磷酸化,高表达DDR1、EPHA2、ROS1酪氨酸激酶活性(n=18,78%),低表达或不表达RTK活性(n=5,22%);癌旁组织EGFR、AXL、EPHB4和PDGFRA表现出最高水平酪氨酸磷酸化;肿瘤组织和癌旁组织磷酸化蛋白种类分布类似。结论:胆管细胞癌组织中酪氨酸激酶激活,DDR1、EPHA2、EGFR和ROS1酪氨酸激酶活性比癌旁组织高表达,可能致胆管细胞癌的发生。
OBJECTIVE: To investigate the changes of tyrosine phosphorylation signal transduction pathway in cholangiocarcinoma tissues and to find new therapeutic targets. Methods: Immunoaffinity, LC-MS / MS analysis identified more than 1000 tyrosine phosphorylation sites in more than 750 different proteins in cholangiocarcinoma patients (n = 23). RESULTS: Cholangiocarcinoma showed the highest levels of tyrosine kinase phosphorylation in DDR1, EPHA2, EGFR and ROS1, high expression of DDR1, EPHA2, ROS1 tyrosine kinase activity (n = 18,78%), low expression or no expression of RTK EGFR, AXL, EPHB4 and PDGFRA showed the highest level of tyrosine phosphorylation. The distribution of phosphorylated proteins in tumor tissues and paracancerous tissues was similar. Conclusion: Tyrosine kinase activation in cholangiocarcinoma tissues and high expression of tyrosine kinase activities of DDR1, EPHA2, EGFR and ROS1 in paracancerous tissues may lead to cholangiocarcinoma.