Objective To study the expression of WWOX gene in bladder carcinoma and its relationship to hypermethylation of WWOX gene CpG island. Methods Methylation specific polymerase chain reaction (MSP) was used to detect the methylation status of WWOX gene. The expression of WWOX gene was detected by real-time RT-PCR,and then the relationship between the expression of WWOX gene and methylation status was analyzed. Results DNA methylation rate of WWOX gene was 35.2% in 54 cases of bladder carcinoma tissues, which was significant different from the adjacent normal tissues with only 7.4% positive (x2=12.43,P < 0.05).DNA methylation rate of WWOX gene increases with pathology grade of cancer( P < 0.05 ).The expression level of WWOX gene in bladder carcinoma was lower than adjacent normal tissues(t =9.73, P < 0.05 ).There was close relationship between the expression of WWOX gene and the methylation status of WWOX gene (r =0.377,P < 0.05). Conclusion Promoter hypermethylation is an important mechanism for the low expression of WWOX gene, which is closely correlated to incidence of bladder carcinoma. The change of methylation status of WWOX gene plays an important role in the carcinogenesis and development of bladder carcinoma.%目的 探讨膀胱移行细胞癌组织中WWOX基因启动子区CpG岛的甲基化状态以及WWOX基因表达缺陷的意义及其与CpG岛甲基化的关系.方法 应用甲基化特异性聚合酶链反应(MSP)和实时荧光定量反转录聚合酶链反应(real-time RT-PCR)分析WWOX基因启动子区甲基化状态和WWOX mRNA表达量及其二者的相关性.结果 54例膀胱癌组织中,WWOX基因启动子区的甲基化率达35.2％,而对应的癌旁正常组织中甲基化率仅为7.4％,二者差异有统计学意义(x2=12.43,P＜0.05).WWOX基因启动子区甲基化率随着癌组织分级的增加逐渐升高(P＜0.05).WWOX mRNA在膀胱癌组织中的表达量明显低于对应的癌旁正常组织中的表达量,二者差异有统计学意义(t=9.73,P＜0.05).WWOX mRNA的表达水平与WWOX基因启动子区的甲基化状态密切相关(r =0.377,P＜0.05).结论 WWOX基因表达的缺失与膀胱癌的发生有密切的关联,WWOX启动子区的异常甲基化是导致膀胱癌组织WWOX mRNA转录受阻的重要原因之一.WWOX启动子区甲基化改变在膀胱移行细胞癌的早期发生发展中有重要作用.
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