膀胱癌中eya4基因启动子区甲基化状态及其临床意义

目的 探讨膀胱癌细胞系和膀胱移行细胞癌组织中EYA转录共激活磷酸酶4(eya4)基因启动子区CpG岛甲基化状态及在临床病理特征中的意义.方法 应用甲基化特异性聚合酶链反应(MSP)检测eya4基因在5株膀胱癌细胞系、1株膀胱永生化上皮细胞系和75例膀胱移行细胞癌组织及癌旁组织,并结合临床病理特征行统计学分析.结果 eya4基因启动子区在5株膀胱癌细胞系中,有4株出现甲基化,其甲基化率为80%;在人正常膀胱细胞系中甲基化阴性.eya4在膀胱癌组织中的甲基化率为70.7%(53/75),显著高于癌旁组织(24%,18/75),差异有统计学意义(x2=32.760,P<0.01).eya4基因启动子区CpG岛甲基化在临床病理特征中如单发膀胱肿瘤与多发膀胱肿瘤相比,直径≤3 cm的膀胱肿瘤与＞3 cm的膀胱肿瘤相比,低级别膀胱肿瘤与高级别膀胱肿瘤相比,浅表性膀胱肿瘤与浸润性膀胱肿瘤相比,差异均有统计学意义(P<0.05),但与年龄和性别无关.结论 基因eya4启动子区甲基化与膀胱癌的发生发展有关,可能作为膀胱移行细胞癌诊断的一个新的标志物.

The methylation status and clinical significance of the promoter of eya4 gene in bladder cancer

Objective To explore the methylation status of the CpG island of eyes absent 4(eya4) promoter and its significance of clinical pathological characteristics in bladder cancer.Methods The promoter methylation status of eya4 gene was examined by methylation specific PCR(MSP) in 5 bladder cancer cell lines and 75 cases of primary bladder transitional cell carcinoma.1 bladder immortalized epithelial cell line and 75 cases of corresponding adjacent tissues were selected as controls.Meanwhile,clinical pathological data of patients were investigated by statistical analysis.Results The promoter of eya4 were detected in 4 cases of 5 bladder cancer cell lines where methyla-tion rate was 80%.While the methylation status was negtive in normal bladder epithelial cell line. The methyla-tion rate of eya4 gene was 70.7% in bladder cancer tissues(53/75) which was significantly more frequent than adjacent tissues(24%,18/75), and the difference was significant(x2=32.760,P<0.01).The methylation status of the CpG island of eya4 promoter was correlated with the clinicopathological features such as tumor diameter,tumor single and mutiple,tumor grade and stage(P<0.05).However, no association was detected between eya4 methylation and age and gender.Conclusion eya4 methylation status which is closely correlated with the occurrence and development of primary bladder transitional cell carcinoma may be used as an independent diagnostic biomarker for patients with different kind of bladder cancer.