膀胱癌WIF-1启动子甲基化状态及其与膀胱癌临床病理关系的研究

Relation between WIF-1 Promoter Methylation and Clinical Pathology of Transitional carcinoma of Bladder

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。

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 WlF-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 WlF-1 was significantly lower in methylated WlF-1 promoter than in unmethyl- ated WIF-1 promoter （P〈0. 001, Kappa value 0. 783）. Concinsions：The inhibition of WIF-1 protein expression in bladder cancer was related to the WlF-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 WlF-1 can be used as a molecular marker to predict the prognosis of patients with TCCB.