循环肿瘤DNA中TSHR、RARβ2和RASSF1A启动子甲基化在甲状腺癌早期诊断中的价值  

The early diagnosis value of TSHR,RARβ2 and RASSF1A promoter methylation in plasma circulating DNA in thyroid carcinoma

作　　者：黄铀新[1] 罗耀玲[2] 任志平[1] 张洪 邓俊华 

机构地区：[1]赣南医学院第一附属医院核医学科,赣州341000 [2]赣南医学院第一附属医院临床研究中心,赣州341000

出　　处：《江西医药》2017年第11期1117-1119,1127,共4页Jiangxi Medical Journal

基　　金：赣南医学院校级课题;编号YB201405;江西省卫生计生委科技计划;编号20161105;江西省教育厅科学技术研究项目;编号150964

摘　　要：目的研究甲状腺结节患者循环肿瘤DNA中TSHR、RARβ2和RASSF1A启动子甲基化状态,探讨其在甲状腺癌早期诊断中的价值。方法采用甲基化特异性PCR(MSP)对16例甲状腺癌患者和59例良性甲状腺结节患者循环肿瘤DNA中TSHR、RARβ2和RASSF1A基因启动子甲基化进行检测,分析其甲基化率与临床病理之间的关系,并评价其临床诊断效能。结果 TSHR在甲状腺癌组甲基化率为56.3%,与良性结节组(37.3%)间差异不显著(P>0.05);RARβ2和RASSF1A在甲状腺癌组甲基化率分别为37.5%和62.5%,均显著高于良性结节组(3.4%,22%),P<0.01。TSHR基因甲基化率在甲状腺癌患者性别、年龄、不同临床分期间均无统计学差异(P>0.05);RARβ2和RASSF1A基因甲基化率在状腺癌患者性别、年龄间无统计学差异,但与不同临床分期有关(P<0.05)。临床诊断效能比较显示:单独检测RASSF1A基因敏感度和Yonden指数最高,而RARβ2特异性最高。三个基因联合检测,其敏感度、特异性和Yonden指数均最高。结论 TSHR、RARβ2和RASSF1A基因异常甲基化与甲状腺癌发生发展相关,三者联合检测有助于甲状腺癌的诊断。Objective To investigate the methylation status of promoters of TSHR,RARβ2 and RASSF1 A,And to investigate the early diagnosis value of thyroid carcinoma. Methods Methylation-specific polymerase chain reaction（MSP） was applied to detect the methylation status of TSHR,RARβ2 and RASSF1 A gene promoters in plasma DNA from 16 patients with thyroid carcinoma and 59 patients with benign thyroid nodules. the relationship between the methylation rate and clinicopathological feature was analyzed. And the clinical diagnostic efficacy was also evaluated. Results The methylation rate of TSHR was no significantiy difference between thyroid cancer group and benign nodules（56.3% vs 37.3%,P 〉0.05）. The methylation rate of RARβ2 and RASSF1 A in thyroid cancer group were significantly higher than that of benign nodules（37.5% vs 3.4%,62.5% vs 22%,all P〈0.01）. There was no significantiy difference between methylation of TSHR and patients＇ sex,age and clinical stages（all P〉 0.05）.There was no statistically difference between methylation of RARβ2 and RASSF1 A and patients＇ sex and age（all P〉0.05）,But but were related to different clinical stages（P〈0.05）. The clinical diagnostic efficacy showed that the RASSF1 A gene sensitivity and Yonden index were the highest,while the specificity of RARβ2 was the highest. The sensitivity,specificity and Yonden index of Combined detection of three genes were highest. Conclusion Aberrant methylation of TSHR,RARβ2 and RASSF1 A genes is associated with the occurrence and development of thyroid cancer,and the combined detection of the three genes is helpful for the diagnosis of thyroid cancer.

关 键 词：甲状腺癌 甲基化 TSHR RARβ2 RASSF1A 

分 类 号：R736.1[医药卫生—肿瘤]