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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。
Objective: To investigate the effect of Wnt-1 (WIF-1) promoter methylation status on WIF-1 protein expression and its clinicopathological relationship with bladder cancer. Methods: The methylation status and WIF-1 protein expression of WIF-1 promoter in 57 cases of bladder cancer were detected by methylation-specific PCR and immunohistochemistry. Normal bladder mucosa and cystitis glandularis tissue as a control. Results: The methylation rates of WIF-1 promoter in bladder cancer, cystitis glandularis and normal bladder tissue were 57.9%, 15.0% and 0 respectively, with statistical significance (P <0.01). The positive rate of WIF-1 promoter methylation was gradually increased with tumor grade and stage (G1, G2, G3 grade were 20.0%, 56.3% and 86.7% respectively; superficial and invasive tumors were 43.8% and 76%, P <0.01). WIF-1 protein expression was significantly lower in promoter methylation of WIF-1 gene in bladder cancer than in unmethylation group (P <0.001, Kappa value was 0.783). The 5-year overall survival between WIF-1 methylated and unmethylated bladder cancer patients was 60.6% and 91.7%, respectively (P <0.05). Conclusion: The loss or decrease of WIF-1 protein expression in bladder cancer is closely related to the WIF-1 promoter methylation. WIF-1 promoter methylation may be an early event in the development of bladder tumor, and is related to the progress of the tumor, which can be used as a molecular marker of prognosis in patients with bladder cancer.