RSK4基因甲基化与甲状腺乳头状癌的相关性研究  

Relationship between methylation of RSK4 gene and papillary thyroid carcinoma

作　　者：尹雅楠 于佳睿 迟静薇[2] 车奎 怀宙阳 王颜刚[1] 王斐[1] 赵世华[1] Yin Yanan;Yu Jiarui;Chi Jingwei;Che Kui;Huai Zhouyang;Wang Yangang;Wang Fei;Zhao Shihua(Department of Endocrinology and Metabolism,the Affiliated Hospital of Qingdao University,Qingdao 266003,China;Laboratory of Thyroid Disease,the Affiliated Hospital of Qingdao University,Qingdao 266003,China)

机构地区：[1]青岛大学附属医院内分泌与代谢病科,266003 [2]青岛大学附属医院甲状腺病实验室,266003

出　　处：《中华内分泌代谢杂志》2019年第12期1031-1036,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：山东省自然科学基金面上项目(ZR2016HM29);山东省重点研发计划项目(2018GSF118051)。

摘　　要：目的探究甲状腺乳头状癌(PTC)核糖体S6蛋白激酶4(RSK4)基因启动子区甲基化状态,分析其与mRNA的表达及与临床特征的相关性。方法收集134例PTC组织及相应134例癌旁甲状腺组织,采用甲基化特异性PCR、亚硫酸氢盐测序法和实时荧光定量PCR分析PTC组织及癌旁组织中RSK4基因甲基化状态与mRNA的表达及与临床特征之间的关系。结果甲基化特异性PCR结果表明,PTC组织中RSK4基因启动子区甲基化阳性率高于癌旁组织(P<0.05),亚硫酸氢盐测序法显示PTC组织中RSK4基因启动子区甲基化率明显高于癌旁组织(P<0.01)。PTC组织中RSK4基因mRNA表达显著低于癌旁组织(P<0.01),且在PTC组织中,甲基化组RSK4基因mRNA表达低于非甲基化组(P<0.01);甲基化的PTC组织RSK4 mRNA表达低于甲基化的癌旁组织(P<0.01),未甲基化的PTC组织RSK4 mRNA表达也低于未甲基化的癌旁组织(P<0.01)。PTC中RSK4基因高甲基化状态与淋巴结转移、TNM分期相关(P<0.05);甲基化组血清促甲状腺激素、甲状腺过氧化物酶抗体、甲状腺球蛋白抗体平均水平高于非甲基化组(P<0.05)。结论RSK4表达降低的机制之一可能为启动子区CpG岛高甲基化,其有可能成为PTC早期诊断及药物治疗的分子靶点。Objective To detect the methylation status of ribosomal S6 kinase 4(RSK4)in papillary thyroid carcinoma(PTC)and to study its correlation with mRNA expression and clinical features.Methods 134 cases PTC tissues and corresponding paracancerous thyroid tissues were collected.DNA methylation status of RSK4 gene in PTC tissues and corresponding paracancerous tissues were analyzed by methylation specific PCR and bisulfite genomic sequencing,and mRNA expression was detected by quantitative realtime PCR.The relationship of DNA methylation status with mRNA expression and clinical features was analyzed.Results The methylation rate of RSK4 in PTC tissues was significantly higher than that in paracancerous tissues by methylation specific PCR(P<0.05)and bisulfite genomic sequencing(P<0.01).The RSK4 mRNA level in PTC tissues was significantly lower than that in paracancerous tissues(P<0.01).In PTC tissues,RSK4 mRNA expression in methylation group was lower than that in unmethylation group(P<0.01).The RSK4 mRNA level in PTC of methylation was lower than that in paracancerous tissues of methylation(P<0.01);the RSK4 mRNA level in PTC of unmethylation was also lower than that in paracancerous tissues of unmethylated ones(P<0.01).There was relationship of RSK4 hypermethylation with lymphatic metastasis and TNM grade(P<0.05).Serum concentrations of thyroid stimulating hormone,thyroid peroxidase antibody,and thyroglobulin antibody in methylation group were higher than those in unmethylation group(P<0.05).Conclusion The hypermethylation of RSK4 promoter′s CpG islands might be one of the mechanisms for poor expression of RSK4 in PTC,which may serve as a molecular target of early diagnosis and treatment.

关 键 词：甲状腺乳头状癌 核糖体S6蛋白激酶4 甲基化 

分 类 号：R73[医药卫生—肿瘤]