[摘要] 目的：以二代测序技术检测胆管细胞癌患者基因变异状态，并分析与患者预后的相关性；方法：收集了自2016 年6月至2018 年6 月3 年收治的40 例确诊胆管细胞癌的患者，进行全外显子二代基因测序（NGS），从中筛选出可能的突变（单碱基突变、结构变异、拷贝数变化、基因融合等），回顾性分析患者一线治疗的疾病控制率（DCR），无进展生存期（PFS）及总生存期（OS），分析患者信号通路及其基因变异与预后的关系。结果：40 例晚期单管细胞癌患者中TP53 基因突变的患者和未发生突变患者的中位PFS和OS分别为11.0 vs 8.3 个月（P=0.332）和14.3 vs 32.9 个月（P=0.041）；而PI3K基因突变的患者和未发生突变患者的中位PFS 和OS分别为8.3 vs 11.0 个月（P=0.285）和14.3 vs 37.0 个月（P=0.020）；mTOR通路突变的患者和未发生突变患者的中位PFS和OS分别为6.3 vs 10.3 个月（P=0.020）和15.6 vs 19.6 个月（P=0.892），通路相关基因发生突变，对生存均没有显著影响。结论：TP53 及PI3K通路激活的胆管细胞癌患者整体预后显著差于未激活的患者，mTOR通路激活及IDH突变对预后及疗效没有显著影响的靶点。

[Abstract] Objective：To detect the gene mutation in cholangiocarcinoma patients using the next generation sequencing (NGS) technology,and to analyze its correlation to the prognosis of the patients. Methods: From June 2016 to June 2018, 40 patients diagnosed with cholangiocarcinoma received NGS examination to screen the possible mutations (single base mutation, structural variation, copy number variation and gene fusion, etc.). The disease control rates (DCR), progression-free survival (PFS) and overall survival (OS) of the patients, who received the first line therapy, were retrospectively reviewed to analyze the relationship between signaling pathway as well as its genetic variation and the prognosis of cholangiocarcinoma patients. Results: The median PFS of patients with and without TP53 mutation was 11.0 and 8.3 months, respectively (P=0.332), while OS was 14.3 and 32.9 months, respectively (P=0.041). The median PFS of patients with and without PI3K mutations was 8.3 and 11.0 months, respectively (P=0.285), while OS was 14.3 and 37.0 months, respectively (P=0.020). The median PFS of patients with and without mTOR pathway mutations was 6.3 and 10.3 months, respectively (P=0.020), while OS was 15.6 and 19.6 months, respectively (P=0.892). There was no significant effect of pathway-related gene mutations on patients’survival. Conclusion: The prognosis of cholangiocarcinoma patients with TP53 and PI3K pathway activation had obviously poor prognosis than those without. No significant difference was observed between the patients with and without mTOR pathway activation and IDH mutation.