甲状腺乳头状癌中hMLH1、NIS和TSHR基因异常甲基化的相互关系及临床意义  

The correlation among hMLH1, NIS and TSHR genes with promoter methylation in papillary thyroid carcinoma and its clinical signi cance

作　　者：陆晓筱[1,2,3] 葛明华[1,2,3] 凌志强[2] 胡思思[2,3] 许敬[4] 郑传铭[4] 谭卓[4] 陈超[4] 

机构地区：[1]温州医学院第一临床医学院,浙江温州325035 [2]浙江省肿瘤医院浙江省肿瘤研究所,浙江杭州310022 [3]浙江省肿瘤医院头颈肿瘤外科,浙江杭州310022 [4]浙江省舟山医院肿瘤科,浙江舟山316000

出　　处：《肿瘤》2013年第5期446-453,共8页Tumor

基　　金：浙江省医药卫生科学研究基金资助项目(编号:2010KYA037、2010KYA031);浙江省卫生高层次创新人才培养工程基金资助项目[编号:浙卫发(2008)134号];卫生部科学研究基金--浙江省医药卫生重大科技计划资助项目(编号:WKJ2012-2-021)

摘　　要：目的:探讨甲状腺乳头状癌(papillary thyroid carcinoma,PTC)组织中错配修复酶人类mutL同系物1(humanmutL homologue1,hMLH1)基因的异常甲基化状态,及其与钠碘同向转运体(sodium iodide symporter,NIS)、甲状腺激素受体(thyroid stimulating hormone receptor,TSHR)基因异常甲基化的相互关系。方法:采用实时荧光定量甲基化特异性聚合酶链反应分别检测152例PTC及对应癌旁正常组织中hMLH1、NIS和TSHR基因启动子甲基化状况。分析hMLH1基因甲基化与各临床病理特征参数之间的关系;hMLH1、NIS和TSHR基因甲基化之间的相关性;以及三者独立、协同作用对PTC进展的影响。结果:152例PTC组织中hMLH1基因的甲基化阳性率(37.5%)高于癌旁正常组织(5.3%)(P<0.05)。hMLH1甲基化与原发灶大小、数量、局部侵犯、T分期、淋巴转移有关(P值均<0.05),而与性别、年龄、病理分期、远处转移无关。hMLH1、NIS和TSHR基因异常甲基化之间存在较弱相关性(r均<0.400);三者的协同作用对PTC各临床病例参数亦无显著影响(P值均>0.05)。结论:hMLH1基因的异常甲基化存在于PTC组织中,可能与肿瘤的进展有关;hMLH1、NIS和TSHR基因的异常甲基化之间不存在相关性,并且它们的独立、协同效应与PTC进展亦不存在相关性。Objective： To investigate the aberrant methylation status of hMI_H1 （human mutL homologue 1） gene in PTC （papillary thyroid carcinoma） tissues, and its correlations with the aberrant methylation of NIS （sodium iodide symporter） and TSHR （thyroid-stimulating hormone receptor） genes. Methods： qMSP （quantitative methylation-specific PCR） was carried out to detect the promoter methylation status of hMLH1, NIS and TSHR genes in PTC tissues and adjacent normal thyroid tissues from 152 patinets with PTC. The correlation between the clinicopathologic characteristics and the promoter methylation status of hMI_H1 gene was analyzed. The relationships among the methylation status of hMLH1, NIS and TSHR genes and their independent or synergistic effects on the progression of PTC were investigated. Results： The promoter methylation rate of hMI_H1 gene in PTC tissues （37.5%） was significantly higher than that in theadjacent normal thyroid tissues （5.3%） （P 〈 0.05）. The promoter methylation of hMIH1 gene in PTC tissues was significantly correlated with the tumor size, number of lesions, local invasion, T stage and lymph node metastasis （P 〈 0.05）, but not correlated with gender, age, clinical TNM stage and distant metastasis （P 〉 0.05）. There was a weak correlation among aberran promoter methylation of hMLH1, NIS and TSHR genes （r 〈 0.400）. The synergistic effect of aberrant promoter methylation of these three genes had no relationship with the clinicopathologic characteristics of PTC （P 〉 0.05）. Conclusion： The aberrant methylation of hMLH1 gene promoter in PTC tissues might be associated with the progression of the tumor. There exists no correlation among the aberrant methylation of hMLH1, NIS and TSHR genes, and their independent or synergistic effect also may not be associated with the progression of PTC.

关 键 词：甲状腺肿瘤 DNA甲基化 HMLH1基因 NIS基因 TSHR基因 

分 类 号：R736.1[医药卫生—肿瘤]