ADAM33在胆管癌中的表达及临床意义  

Expression of ADAM33 in cholangiocarcinoma and its clinical significance

作　　者：张国华[1] 谭大勇[1] 李娜[1] 王晓临[1] 王威力 ZHANG Guohua;TAN Dayong;LI Na;WANG Xiaolin;WANG Weili.(First Department of Hepatobiliary and Pancreatic, Affiliated Hospital of Qinghai University (Affiliated Tumor Hospital of Qinghai University), Xining 810001, China)

机构地区：[1]青海大学附属医院(青海大学附属肿瘤医院)肝胆胰一科,西宁810001

出　　处：《临床肿瘤学杂志》2020年第10期895-899,共5页Chinese Clinical Oncology

基　　金：青海大学附属医院中青年科研基金一般资助项目(ASRF-2017-YB-08)。

摘　　要：目的探讨去整合素-金属蛋白酶33(ADAM33)在胆管癌中表达及其与临床病理特征和预后的关系。方法基于TCGA数据库比较胆管癌组织和癌旁正常组织中ADAM33基因表达和甲基化程度。另选取2016年1月至2019年10月青海大学附属医院收治的90例胆管癌患者手术组织标本,采用免疫组化染色和甲基化DNA免疫共沉淀-定量PCR(MeDIP-QPCR)法检测肿瘤组织和癌旁正常组织中ADAM33蛋白表达和基因甲基化程度。分析ADAM33蛋白表达与临床病理特征和预后的关系。结果TCGA数据集9例癌旁正常组织和36例胆管癌组织中的ADAM33基因表达和甲基化水平差异无统计学意义(P>0.05)。90例胆管癌组织中ADAM33蛋白阳性表达率(68.9%vs.31.1%)和甲基化程度(0.96±0.54 vs.0.70±0.56)均高于癌旁正常组织(P<0.05)。不同ADAM33蛋白表达组中ADAM33基因甲基化程度差异无统计学意义(0.91±0.54 vs.1.06±0.55,P>0.05)。ADAM33蛋白表达与TNM分期、淋巴结转移、血管侵犯以及预后有关(均P<0.05);ADAM33蛋白阳性表达是影响患者术后预后不良的独立危险因素(P<0.05)。结论胆管癌组织中ADAM33蛋白表达上调,且与预后不良有关,但并不受ADAM33基因启动子甲基化调控的影响。Objective To investigate the expression of disintegrin and metalloproteinase 33(ADAM33)in cholangiocarcinoma and its relationship with clinical characteristics and prognosis.Methods The expressions of ADAM33 mRNA and promoter methylation were compared in bile duct carcinoma tissues and adjacent normal tissues based on TCGA database.In addition,surgical tissue samples from 90 patients with cholangiocarcinoma admitted to the Affiliated Hospital of Qinghai University from January 2016 to October 2019 were selected,and ADAM33 protein expression and gene methylation degree in tumor tissues and adjacent normal tissues were detected by immunohistochemistry and methylated DNA immunoco-precipitation-quantitative PCR(MeDIP-QPCR).The relationship between ADAM33 expression and clinicopathological characteristics and prognosis was analyzed.Results There was no significant difference in ADAM33 gene expression and methylation level between 9 TCGA cases and 36 cases of cholangiocarcinoma tissues(P>0.05).ADAM33 positive expression rate(68.9%vs.31.1%)and methylation degree(0.96±0.54 vs.0.70±0.56)were higher in 90 cases of cholangiocarcinoma than in adjacent normal tissues(P<0.05).There was no significant difference in the methylation degree of ADAM33 gene in different ADAM33 protein expression tissues(0.91±0.54 vs.1.06±0.55,P>0.05).ADAM33 expression was associated with TNM stage,lymph node metastasis,vascular invasion and prognosis(all P<0.05).ADAM33 positive expression is an independent risk factor for poor postoperative prognosis(P<0.05).Conclusion ADAM33 protein expression is increased in cholangiocarcinoma tissues,which is related to the poor prognosis of patients,but it is not affected by the regulation of ADAM33 gene promoter methylation.

关 键 词：胆管癌 ADAM33 DNA甲基化 临床病理特征 预后 

分 类 号：R735.8[医药卫生—肿瘤]