甲状腺乳头状癌中RUNX3基因启动子甲基化及其蛋白表达的研究

Methylation and expression of RUNX3 gene promoter in papillary thyroid carcinoma

目的探讨甲状腺乳头状癌（papillary thyroid carcinoma，PTC）组织中runt相关转录因子3（runt—related transcription factor3，RUNX3）基因启动子甲基化及其与蛋白的表达。方法采用甲基化特异性聚合酶链反应及免疫组化方法检测56例PTC及其对应的癌旁组织中RUNX3基因启动子甲基化及其蛋白的表达。结果在癌旁组织中，无一例出现RUNX3基因启动子甲基化，而在PTC组织中20例出现甲基化，且甲基化状态与PTC的TNM分期、病理分级及淋巴转移有关（P值均〈0．05）；癌旁组织和PTC中，RUNX3蛋白表达的阳性率分别为100．0％和60．7％，P〈0．05。在PTC组中，在病理分级I级和Ⅱ级组中，RUNX3蛋白阳性率分别为70．0％和37．5％，淋巴转移阳性和阴性组分别为46．7％和76．9％，差异均有统计学意义（P值均〈0．05）；RUNX3基因启动子甲基化与其蛋白表达有明显的相关性（x2=21．62，P〈0．01）。结论RUNX3基因启动子甲基化是该基因失活的重要机制之一；RUNX3蛋白表达下调可能对甲状腺乳头状癌的发生、发展具有重要作用。

Objective To study the relationship between status of methylation of human runt-related transcription factor 3 （RUNX3） gene promoter in papillary thyroid carcinoma （PTC）. Methods Methylation-specific PCR and immunohistochemical SP technique were used to detect the methylation of RUNX3 gene promoter and expression of its protein in 56 cases of PTC and their matched adjacent non- carceious epithelium（NCE）. Results In NCE, there was no methylation of RUNX3 gene promoter, while in PTC the methylation rate was 35.7% （20/56） , which was related to the tumor TNM stage, pathological grade and lymph node metastasis （P 〈 0. 05）. The positive rates of RUNX3 protein expression in NCE and PTC were 100. 0% and 60. 7% , respectively, with a significant difference （ X2 = 27. 378, P 〈 0. 05 ）. In PTC, the positive rates of RUNX3 protein expression in grade I and grade II were 70. 0% and 37.5% , respectively（ P 〈 0. 05 ） ; the rates were 46. 7% and 76. 9% in lymph node metastasis group and no metastasis group, respectively （P 〈 0.05 ）. Moreover, there was a distinct correlation between methylation of RUNX3 gene promoter and expression of its protein （ X2 = 21.62, P 〈 0. 01 ）. Conclusions Methylation of promoter might be one of the important factors of inactivation of RUNX3 gene, and might play an important role in carcinogenesis and progression of PTC.