miR-200c/ZEB1/E-cadherin轴在胆管癌转移侵袭中的作用及对胆管癌预后评估的价值  

Value of miR-200c/ZEB1/E-cadherin axis in the metastasis and invasion of cholangiocarcinoma and its implications for the prognosis evaluation of cholangiocarcinoma

作　　者：潘超[1] 许蔚[1] 刘子君[1] 陶平[1] 杨士勇[1] PAN Chao;XU Wei;LIU Zijun;TAO Ping;YANG Shiyong(Department of General Surgery,Nanjing's Hospital of Nanjing Medical University/Nanjing First Hospital,Jiangsu Nanjing 210006,China)

机构地区：[1]南京医科大学附属南京医院/南京市第一医院普外科,江苏南京210006

出　　处：《现代肿瘤医学》2024年第7期1287-1294,共8页Journal of Modern Oncology

基　　金：江苏省南京市卫计委一般性课题(编号:YKK20115)。

摘　　要：目的:探讨微小RNA-200c(miR-200c)/锌指转录因子(ZEB1)/E-钙黏蛋白(E-cadherin)在胆管癌(HCCA)转移、侵袭中的作用及对HCCA预后评估的临床价值。方法:选取2020年08月至2022年12月间我院收治的胆管癌患者36例为研究对象,同时选取胆管良性疾病患者(胆总管结石或胆管良性狭窄)20例作为对照。采用原位杂交、实时荧光定量PCR检测miR-200c在HCCA患者组织及血清中的表达;生存曲线分析miR-200c表达与总生存期的相关性;Transwell实验检测细胞的迁移及侵袭能力;免疫印迹检测ZEB1及E-cadherin蛋白的表达。体内研究构建裸鼠成瘤实验,采用免疫组化检测ZEB1及E-cadherin蛋白的表达;Tunel技术检测组织中的凋亡情况。受试者工作特征(ROC)曲线评估生物标志物对胆管癌预后的诊断效能。结果:miR-200c低表达于HCCA组织及血清中;生存曲线分析显示,miR-200c表达与患者的总生存期呈正相关性,TNM分期与患者的总生存期呈负相关性;miR-200c mimics抑制了胆管癌细胞的迁移和侵袭能力,并降低ZEB1表达而诱导E-cadherin表达;转染ZEB1逆转miR-200c的作用效应,促进胆管癌细胞的迁移和侵袭特性,抑制胆管癌细胞的凋亡。CA199、CEA和miR-200c联合检测诊断胆管癌预后的ROC曲线下面积为0.892,灵敏度0.8611,特异度0.8000。结论:miR-200c/ZEB1/Ecadherin轴参与胆管癌的转移侵袭;CA199、CEA和miR-200c联合检测对胆管癌预后的诊断效能良好,对临床胆管癌的治疗策略具有重要指导价值。Objective:To investigate the role of microRNA 200c(miR-200c)/Zinc finger E-box binding homeobox 1(ZEB1)/E-cadherin in the metastasis and invasion of hilar cholangiocarcinoma(HCCA)and its clinical value in evaluating the prognosis of HCCA.Methods:Thirty six patients with cholangiocarcinoma admitted to our hospital from August 2020 to December 2022 were selected as research objects,and 20 patients with benign biliary diseases(common bile duct stones or benign biliary strictures)were selected as controls.In situ hybridization and real-time fluorescence quantitative PCR were used to detect the expression of miR-200c in the tissues and serum of HCCA patients.Survival curve analysis of the correlation between miR-200c expression and overall survival.Transwell experiment was used to detect the cells migration and invasion ability.Immunoblotting was used to detect the expression of ZEB1 and E-cadherin proteins.In vivo research was conducted to construct a nude mouse tumor formation experiment,and immunohistochemistry was used to detect the expression of ZEB1 and E-cadherin proteins.Tunel technology is used to detect apoptosis in cholangiocarcinoma tumor tissue.The diagnostic efficacy of biomarkers in the prognosis of HCCA was evaluated by receiver operating characteristic(ROC)curve.Results:miR-200c was low expressed in HCCA tissues and serum.Survival curve analysis showed a significant positive correlation between miR-200c expression and overall survival of patients,and a significant negative correlation between TNM staging and overall survival of patients.miR-200c mimics inhibited the migration and invasion of cholangiocarcinoma cells,reduced the expression of ZEB1 and induced the expression of E-cadherin.The transfection of ZEB1 reversed the effect of miR-200c,promoted the migration and invasion of cholangiocarcinoma cells,and inhibited the apoptosis of cholangiocarcinoma cells.The area under the ROC of CA199,CEA and miR-200c for the diagnosis of prognosis of HCCA was 0.892,the sensitivity was 0.8611,and the specificit

关 键 词：胆管癌 微小RNA-200c(miR-200c) 锌指转录因子(ZEB1) E-钙黏蛋白(E-cadherin) 迁移 侵袭 

分 类 号：R735.8[医药卫生—肿瘤]