甲状腺乳头状癌组织中TSHR基因启动子甲基化及其临床意义

Methylation of TSHR Gene Promoter in Papillary Thyroid Carcinoma and its Clinical Significance

[目的]探讨甲状腺乳头状癌(papillary thyroid cancer,PTC)组织中TSHR基因启动子区甲基化程度及其临床意义。[方法]采用甲基化特异性聚合酶链反应(Methylation-Specific Polymerase chain reaction,MSP)法检测100例PTC组织及其癌旁组织中TSHR基因启动子甲基化状态,并结合患者的临床病理特征和随访信息分析TSHR与PTC进展及预后的关系。[结果]100例PTC组织中TSHR基因启动子甲基化率为77%,明显高于癌旁组织的7%(P=0.002)。TSHR基因甲基化程度与患者初诊年龄、原发灶大小、数量、腺外侵犯、淋巴转移、TNM分期呈正相关(P<0.05);而与患者性别、T分期无关(P>0.05)。单因素生存分析显示TSHR基因甲基化预示更短的无病生存时间,而多因素生存分析显示TSHR基因甲基化不是PTC患者无病生存的独立影响因素。[结论 ]TSHR基因启动子区甲基化是PTC组织中频发的分子事件,与肿瘤的进展相关并提示PTC患者的不良预后。

[Objective] To investigate the methylation status of TSHR gene promoter region in thyroid papillary thyroid carcinoma （PTC） and its clinical significance. [ Methods ] The methylation status of TSHR gene promoter was detected by methylation-specific polymerase chain reaction （MSP） in 100 cases of PTC tissue and the paired adjacent normal tissues. The correlation of TSHR methylation with the tumor progression and prognosis was analyzed. [Results] The methy- lation rate of TSHR gene promoter in PTC was 77% ,which was significantly higher than that in matched normal tissue （P=0.002）. There was a positive correlation of the methylation of TSHR gene with the age,the size of primary tumor,the number of primary tumor,the tumor invasion, lymphatic metastasis and TNM stage（P〈0.05）,but not with gender and T stage （P〉0.05）. Univari- ate survival analysis showed that TSHR gene methylation was associated with shorter disease-free survival time. Multivariate survival analysis showed that TSHR gene methylation was not associated with the survival of patients. [ Conclusion ] The methylation of TSHR gene promoter region is a frequent molecular event in PTC tissue, which is associated with the tumor progression and may suggest a poor prognosis in PTC patients.