目的应用Meta分析方法综合评价促甲状腺激素受体(TSHR)基因的甲基化与人甲状腺乳头状癌的关联,为预防和诊治甲状腺乳头状癌提供参考。方法检索纳入2000年1月q013年4月发表的8篇有关TSHR基因甲基化和人甲状腺乳头状癌关系的中英文文献,应用随机效应模型和固定效应模型对其进行综合的定量分析。结果来自8篇文献的583份样本被纳入Meta分析,甲状腺乳头状癌样本中TSHR基因发生甲基化数与对照组相比的合并OR值为4.57[95%CI(1.68,12.43),P〈0.01]。分层分析(对照类型、国家、年龄、肿瘤分期、淋巴结转移)以及回归分析用于探索异质性的来源以及可能的危险因素,结果显示,在中国人群中和年龄小于45岁的甲状腺乳头状癌人群中[OR=9.18,95%CI(5.19,16.23),P〈0.01]以及在非自体组织为对照的研究中[OR=8.51,95%CI(3.72,19.46),P〈0.01],TSHR基因的甲基化发生率均较高。TSHR基因甲基化在各期甲状腺癌中均可出现,TSHR基因甲基化发生率在肿瘤中晚期阶段[OR=14.12,95%CI(2.93,68.18)]高于早期[OR:6.01,95%CI(3.21,11.28)],与淋巴结转移也存在关联(OR=14.29,95%CI(2.47,82.75),P〈0.01]。本研究未观察到存在发表偏倚(t=-0.01,P〉0.05),具有较好的代表性。结论TSHR基因为甲状腺乳头状癌抑制基因,其甲基化的发生与甲状腺乳头状癌具有很强的相关性,可作为一个潜在的分子诊断标志物。
Objective To assess the association between methylation of thyroid stimulating hormone receptor (TSHR) gene and human papillary thyroid carcinoma by using meta- analysis method, so as to provide a reference for the prevention, di- agnosis and treatment of papillary thyroid carcinoma. Methods Eight papers studying on the relationship between TSHR gene methylation and papillary thyroid carcinoma published in English or Chinese from January 2000 to April 2013 were retrieved, and synthetically quantified analysis was synthetically conducted by using random effect model and fixed effect model. Reslflts A total of 583 samples from the eight studies were included in the meta - analysis. A significant association was observed between TSHR gene methylation and papillary thyroid carcinoma, with a pooled odds ratio (OR) of 4. 57, 95% CI (1.68, 12. 43), P 〈 0.01. Subgroup analysis including control type, country, age, TNM and lymphatic metastasis, and meta -regression analysis were performed to determine the source of the heterogeneity and possible risk factors. The results showed that, in Chinese popula- tion and those people those age less than 45 [ OR = 9. 18, 95% CI ( 5. 19, 16. 23 ), P 〈 0.01 ] and in the studies with non - autogenous tissues as the control [ OR = 8.51, 95 % CI ( 3.72, 19.46 ), P 〈 0.01 ], the prevalence of TSHR gene methylation was higher. The TSHR gene methylation could occur at any state of the thyroid carcinoma. Its prevalence at the meddle stage [ OR =14. 12, 95%CI (2.93, 68.18)1 was significantly higher than that at the early stage [OR = 6.01, 95% CI (3.21, 11.28) ], and it was associated with the lymphatic metastasis [ OR = 14. 29, 95 % CI ( 2.47, 82. 75 ), P 〈 0.01 ]. No publi- cation bias was detected ( t = - 0. 01, P 〉 0.05 ) . Conclusion TSHR gene is a suppressor gene of papillary thyroid carcino- ma. Its methylation has a close association with papillary thyroid carcinoma, so it may be taken as a candidate of early molecular diagnosis of papilla