膀胱移行细胞癌尿沉淀细胞INK4a和ARF基因启动子异常甲基化及临床意义  

Detection of promoter methylated INK4a/ARF gene in urine sediments of bladder cancer patients

作　　者：廖于峰[1] 马建波[1] 魏任雄[1] 贾广成[2] 

机构地区：[1]浙江省宁波市第二医院检验中心,浙江宁波315010 [2]浙江省宁波市第二医院泌尿外科,浙江宁波315010

出　　处：《中国卫生检验杂志》2010年第8期1946-1948,共3页Chinese Journal of Health Laboratory Technology

基　　金：浙江宁波市医学科技计划项目(2007010)

摘　　要：目的:探讨膀胱癌患者尿沉淀细胞中INK4a/ARF基因启动子CpG岛的甲基化状况及其临床意义。方法:采用甲基化特异性PCR(MSP)的方法检测35例膀胱癌患者尿沉淀细胞INK4a/ARF基因启动子甲基化异常频率,同时以30例非肿瘤性泌尿系疾病患者作为对照。卡方检验(χ2)分析其甲基化程度与膀胱癌临床病理参数之间的关系。结果:膀胱癌尿沉淀细胞INK4a/ARF基因甲基化阳性率分别为25.7%(9/35)和42.9%(15/35),两个基因联合时甲基化阳性率为48.6%(17/35)。浸润性(≥pT2)和表浅性(≤pT1)膀胱癌尿沉淀细胞INK4A/ARF基因甲基化阳性率之间的差异有统计学意义(P<0.01)。INK4a/ARF基因甲基化在不同病理分级、膀胱癌初发与复发和不同性别间其差异无统计学意义(P>0.05)。INK4a与ARF基因启动子甲基化呈正相关关系(r=0.415,P<0.05)。结论:INK4a/ARF基因甲基化不仅是膀胱癌发生的早期事件,而且与膀胱癌的浸润性发展相关。尿沉淀细胞INK4a/ARF基因启动子异常甲基化状态可作为非侵入性诊断膀胱癌并且判断其预后的分子标志物。Objective：To evaluate promoter methylation of INK4a/ARF and its clinical significance.Methods：A total of 35 patients with bladder cancer and 30 benign diseases as controls are enrolled into this study.The hypermethylated status of INK4a/ARF were evaluated with methylation-specific polymerase chain reaction in DNA extracted from urine in patients and controls.Results：The methylation rate for INK4a and ARF was 25.7% and 42.9%,respectively,in urne sediments of bladder cancers.Diagnostic sensitivity was 48.6% for combining INK4a andARF.The incidence of INK4a and ARF methylation was significantly higher in patients with invasive（≥pT2） than superficial bladder cancer（≤pT1）（P=0.001 and P=0.000,respectively）.Methylation status of INK4a/ARF had no correlation with gender,tumor grade,primary and recurrent tumors（P〉0.05）.Promoter methylation of INK4a was highly correlated with ARF（r=0.415）.Conclusion：MSP analysis of INK4a/ARF can be used as a good biomarker for bladder cancer diagnosis,staging and prognosis prediction.

关 键 词：膀胱移行细胞癌 INK4A ARF DNA甲基化 尿沉淀细胞 

分 类 号：R737.1[医药卫生—肿瘤]