【摘要】 目的:研究Wnt抑制因子1(WIF-1)启动子甲基化状态对WIF-1蛋白表达的影响及其与膀胱癌的临床病理关系。方法:采用甲基化特异性PCR方法和免疫组织化学方法检测57例膀胱癌WIF-1启动子甲基化状态和WIF-1蛋白表达情况。以正常膀胱黏膜及腺性膀胱炎组织为对照。结果:膀胱癌、腺性膀胱炎和正常膀胱组织WIF-1启动子甲基化率分别为57.9%,15.0%和0,差异有统计学意义(P<0.01)。WIF-1启动子甲基化阳性率随肿瘤分级、分期的增加逐渐升高(G1、G2、G3级分别为20.0%、56.3%和86.7%;浅表性和浸润性肿瘤分别为43.8%和76%,P<0.01)。膀胱癌组织WIF-1基因启动子甲基化时WIF-1蛋白表达率明显低于未甲基化组(P<0.001,Kappa值为0.783)。WIF-1甲基化与未甲基化组膀胱癌患者之间的5年总生存率分别为60.6%和91.7%(P<0.05)。结论:膀胱癌WIF-1蛋白表达缺失或减少与WIF-1启动子甲基化密切相关。WIF-1启动子甲基化可能是膀胱肿瘤发生的早期事件,而且与肿瘤的进展有关,可作为膀胱癌患者预后判断分子标志物。更多还原

【Abstract】 Objective:To study the Wnt inhibitory factor(WIF-1)promoter methylation and its effect on the protein expression and its relation with clinical pathology of transitional carcinoma of bladder(TCCB).Methods:Methylation-specific PCR was used to detect the methylation status of WIF-1 promoter,and immunohistochemistry was applied to measure WIF-1 protein expression of bladder cancer tissues of 57 patients.Epithelial tissues of normal bladder and glandular cystitis were also tested as control.Results:The methylation rate of bladder cancer,glandular cystitis and normal bladder tissue were 57.9%,15% and 0,respectively(P<0.01).The methylation rate significantly increased with tumor grade and stage.The rates of 20%,56.3% and 86.7% were found in grade G1,G2 and G3(P<0.01),and 43.8% and 76% in superficial and invasive bladder cancers,respectively(P<0.05).The protein expression of WIF-1 was significantly lower in methylated WIF-1 promoter than in unmethylated WIF-1 promoter(P<0.001,Kappa value 0.783).Conclusions:The inhibition of WIF-1 protein expression in bladder cancer was related to the WIF-1 promoter methylation.WIF-1 promoter methylation may have an important role on the early stage of carcinogenesis of TCCB,and may also involve in tumor progression.The methylation rate of WIF-1 can be used as a molecular marker to predict the prognosis of patients with TCCB.更多还原