促甲状腺激素受体基因启动子区甲基化与乳头状甲状腺癌的关系研究

A Study on the Promoter Hypermethylation of TSHR in Human Papillary Thyroid Carcinoma

目的观察促甲状腺激素受体(TSHR)在乳头状甲状腺癌(PTC)中的表达,分析其基因启动子区甲基化与肿瘤发生的关系。方法选择50例PTC和32例良性甲状腺肿瘤患者(对照组,包括20例结节性甲状腺肿和12例甲状腺腺瘤患者),对两组患者手术获取的标本提取RNA后,逆转录为cDNA,进行PCR,检测TSHR基因的表达情况;运用甲基化特异性PCR(MSP)法检测上述组织中TSHR基因启动子区甲基化的情况。结果PTC组患者中,有34例(68.0%)TSHR基因启动子发生甲基化,16例(32.0%)TSHR基因mRNA表达缺失;对照组患者中,有7例(21.9%)TSHR基因启动子发生甲基化,4例(12.5%)TSHR基因mRNA表达缺失,PTC组织TSHR基因启动子区甲基化率及TSHR基因mRNA表达缺失率均显著高于对照组,差异有统计学意义(χ2值分别为16.61和4.02,P<0.05)。34例发生了TSHR基因启动子区甲基化的PTC患者中,有14例(41.2%)TSHRmRNA表达缺失;16例未发生甲基化的PTC患者中,2例(12.5%)发生了mRNA表达缺失,二者mRNA表达缺失率间差异有统计学意义(χ2=4.11,P<0.05)。结论PTC患者TSHR基因启动子甲基化发生率显著高于良性甲状腺肿瘤患者,而TSHR基因mRNA的表达则较良性甲状腺肿瘤降低;推测TSHR基因启动子区甲基化可能与PTC的发生、发展相关。

Objective To study the expression of the tumor suppressor gene TSHR （thyroid stimulating hormone receptor, TSHR） in PTC （papillary thyroid carcinoma, PTC）, and the correlation between the expression and the aberrant promoter methylation of TSHR gene. Methods RT - PCR was used to detect the mRNA expression of TSHR in 50 cases of PTC, 20 cases of nodular goiter and 12 cases of thyroid adenoma tissue. We examined the promoter methylation status of TSHR gene by using methylation - specific PCR technique （MSP）. Results 34 cases in 50 cases of PTC patients （68.0%） were detected hypermethylation of TSHR gene in promoter region, 7 cases in 32 cases of controls （21.9%） were detected hypermethylation of TSHR gene in promoter region, the rate of methylation of TSHR promoter in PTC was significantly higher than that in controls （ X^2 =16. 61, P〈0. 05）. TSHR expression was not detected in 16 cases of the 50 cases of PTC and in 4 cases of the 32 cases of controls, there was an obviously lower expression of TSHR in PTC （ X^2 = 4.02, P 〈 0.05 ）. Conclusion Methylation of TSHR gene in promoter region is a common molecule event and may be invovled in the genesis and development of human PTC.