华支睾吸虫感染的肝内胆管癌上皮组织miR-215与PTEN表达的关系  

Expression of miR-215 and PTEN in intrahepatic cholangiocarcinoma tissue with clonorchis sinensis infection

作　　者：刘清波[1] 王卫东[1] 陈小伍[1] 何威[1] 陈坚平[1] 马靖[1] 吴国标[1] 

机构地区：[1]顺德区第一人民医院普外二区,广东佛山528300

出　　处：《中华肿瘤防治杂志》2016年第8期515-519,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：佛山市科技局立项资助项目(2014AB002163)

摘　　要：目的广东顺德地区华支睾吸虫(Clonorchis sinensis,CS)感染率高,华支睾吸虫感染与肝内胆管癌(intrahepatic cholangiocarcinoma,ICC)发病密切相关;探讨伴或不伴CS感染的ICC组织及癌旁胆管上皮组织中miR-215和PTEN表达关系,为揭示ICC发病的分子机制提供依据。方法收集2010-01-2015-04顺德区第一人民医院治疗的ICC患者40例,其中采用不规则性肝段或肝叶切除16例,姑息性肝段切除24例,以及同期伴或不伴CS感染的外伤性肝段切除肝内胆管组织各10例;酶联免疫吸附法检测患者血清CSIgG滴度;实时定量PCR法检测胆管癌组织和胆管上皮组织miR-215表达水平;免疫组织化学法检测胆管癌组织和癌旁胆管上皮组织PTEN蛋白表达水平;miRNA靶基因预测的生物信息学数据库分析miR-215靶向PTEN的分子机制。结果伴CS感染的ICC(1.46±0.24)及癌旁组织(1.36±0.28)的miR-215表达水平,显著高于不伴CS感染的ICC(0.45±0.17)及癌旁组织(0.57±0.21),F=66.01,P<0.001;伴CS感染的胆管组织miR-215表达水平为1.16±0.08,显著高于不伴CS感染的胆管组织的0.37±0.05,t=8.156,P<0.001;ICC组织miR-215表达与血清CS IgG滴度呈显著正相关,r=0.77,P=0.001 2;伴CS感染的ICC组织PTEN阳性表达率为17.24%(5/29),显著低于不伴CS感染感染的ICC组织的54.55%(5/11),χ2=5.566,P=0.018;ICC组织中PTEN表达与miR-215表达呈负相关,r=-0.692,P=0.002。结论 CS肝内感染的胆管上皮组织miR-215表达上调通常伴随抑瘤基因PTEN的表达下调,CS异位高表达的miRNA可能参与胆管癌发病过程。OBJECTIVE Clonorchis Sinensis infection rate in Guangdong Shunde is high,and its infection positively correlated to the pathogenesis of Intrahepatic Cholangiocarcinoma.This study is to determine the relationship of miR-215 and PTEN expression in intrahepatic cholangiocarcinoma tissues,adjacent intrahepatic cholangiocarcinoma tissues,with or without Clonorchis sinensis infection,and to lay a base for the molecular mechanism of miR-215 in Cholangiocarcinoma.METHODS Data and specimens were collected from January 2010 to April 2015 in the Department of general surgery,No.1Hospital of Shunde.Totally 40 cases of intrahepatic cholangiocarcinoma were included which were surgically treated by irregular liver lobectomy or segmentectomy（16/40）and palliative liver segmentectomy（24/40）,and intrahepatic bile duct tissue as the internal control grouped by traumatic liver segmentectomy in the same period with or without infection of Clonorchis Sinensis（10cases）.Human serum IgG titer of Clonorchis sinensis was detected by ELISA.miR-215 expression in intrahepatic bile duct tissue was detected using qRT-PCR.PTEN protein was detected by immunohistochemistry in intrahepatic cholangiocarcinoma and normal intrahepatic bile duct tissue.The molecular mechanism of miR-215 targeting PTEN was analysed using four public database of miRNA-target prediction.RESULTS miR-215 expression in intrahepatic cholangiocarcinoma（1.46±0.24）and adjacent non-cancerous tissue（1.36±0.28）with Clonorchis sinensis infection was significantly higher than those（0.45±0.17,0.57±0.21,respectively）without Clonorchis sinensis infection（F=66.01,P〈0.001）.miR-215 expression in the internal control grouped by traumatic liver segmentectomy（1.16±0.08）with Clonorchis sinensis infection was significantly higher than those（0.37±0.05）without Clonorchis sinensis infection（t=8.156,P〈0.001）.miR-215 expression positively correlated to serum Clonorchis sinensis IgG titers（r=0.77,P=0.001 2）;miRNA-target prediction analysis indicate

关 键 词：肝内胆管癌 华支睾吸虫 miR-215 PTEN 相关 

分 类 号：R735.8[医药卫生—肿瘤]