涎腺腺样囊性癌中RUNX3的表达、甲基化状态及其临床意义

目的 探讨RUNX3基因的异常表达与人涎腺腺样囊性癌发生、发展的关系.方法 以定量甲基化特异性PCR（qM-SP）法检测41例涎腺腺样囊性癌及其相应的正常涎腺组织中RUNX3基因的甲基化状态,并比较RUNX3基因启动子甲基化与腺样囊性癌临床病理因素之间的相关性.同时用Western blot法检测其中19例腺样囊性癌及其匹配的正常涎腺组织中RUNX3蛋白的表达,以分析RUNX3基因启动子甲基化对蛋白表达的影响.结果 实时定量qMSP结果显示腺样囊性癌及其相应正常涎腺组织中其RUNX3基因甲基化阳性率分别为（48.81±5.81）%和（27.98±3.84）%,两者存在显著差异（P＜0.001）.Western blot结果显示腺样囊性癌中RUNX3蛋白的表达量显著低于匹配的正常涎腺组织中的表达（P＜0.001）,提示RUNX3基因甲基化是引起RUNX3蛋白表达下调的原因之一,也与肿瘤的发生相关.结论 RUNX3基因启动子5＇-CpG岛高甲基化在人涎腺腺样囊性癌中是一高频分子事件,与该基因的表达缺失显著相关,是RUNX3基因表达缺失的主要机制之一.RUNX3基因甲基化与腺样囊性癌的发生存在密切联系.

Expression and methylation status of RUNX3 gene in adenoid cystic carcinoma of salivary gland and its clinical significance

Objective To investigate the expression and methylation of RUNX3 gene and its relationship with adenoid cystic carcinoma （ACC） of salivary gland. Methods The quantitative MSP method was used to detect the methylation status of 5＇-CpG island in RUNX3 promoter region in 41 salivary gland ACC samples and the corresponding non-neoplastic salivary glands. The western blot method was used for detecting the expression of RUNX3 protein in 19 of 41 ACC samples. The association among the methylation of RUNX3 gene, RUNX3 protein expression and the clinicopathological parameters of ACCs, was analyzed. Results The results of qMSP showed that the methylation rate was 48.81 ± 5.81% and 27.98 ± 3.84% in 41 salivary gland ACC samples and the corresponding non-neoplastic salivary glands, respectively （P〈0.001）. Western blot results revealed that the RUNX3 protein level in ACC was significantly lower than that in normal salivary glands （P〈0.001）. Conclusion RUNX3 gene promoter 5＇-CpG island hypermethylation may is a frequency molecular event in ACCs associated with down regulation of RUNX3 protein, which might be related to the tumorigenesis of ACCs.