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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 investigate the methylation status of INK4a / ARF promoter CpG island in urinary sediment cells of patients with bladder cancer and its clinical significance. Methods: Methylation-specific PCR (MSP) was used to detect the abnormal methylation frequency of INK4a / ARF gene promoter in 35 cases of bladder cancer and 30 cases of non-neoplastic urological diseases as controls. Chi-square test (χ2) analysis of the relationship between methylation and clinicopathological parameters of bladder cancer. Results: The positive rates of INK4a / ARF gene methylation in urinary sedimentary cells were 25.7% (9/35) and 42.9% (15/35), respectively. The positive rate of methylation was 48.6% 35). The positive rates of methylation of INK4A / ARF gene in invasiveness (≥pT2) and superficial (≤pT1) bladder cancer urine sediment cells were statistically significant (P <0.01). The methylation of INK4a / ARF gene was not statistically significant in different pathological grades, primary bladder cancer recurrence and different gender (P> 0.05). There was a positive correlation between INK4a and ARF promoter methylation (r = 0.415, P <0.05). Conclusion: Methylation of INK4a / ARF gene is not only an early event in bladder cancer, but also associated with the invasiveness of bladder cancer. Urinary sediment cell INK4a / ARF gene promoter abnormal methylation status can be used as non-invasive diagnosis of bladder cancer and determine the prognosis of molecular markers.