膀胱癌尿沉渣PTEN基因启动子CpG岛异常甲基化研究

Detection of Promoter Methylated PTEN Gene in Urine Sediments in Patients with Bladder Cancer

目的探讨膀胱癌患者尿沉渣细胞中PTEN基因启动子CpG岛的甲基化状况及其临床意义。方法收集临床病理确诊39例膀胱癌,采用甲基化特异PCR(MSP)的方法,检测膀胱癌肿瘤组织和配对的尿沉渣PTEN基因启动子CpG岛的甲基化异常频率,同时以45例非肿瘤性泌尿系疾病患者及14例健康志愿者作为对照。结果膀胱癌肿瘤组织和配对的尿沉渣PTEN基因启动子甲基化阳性率分别为53.8%(21/39)和48.7%(19/39),两者密切相关(r=0.381,P=0.017)。膀胱癌组尿沉渣PTEN基因启动子甲基化阳性率(48.7%,19/39)显著高于非肿瘤组(11.1%,5/45)(2χ=15.37,P=0.000),非肿瘤组与志愿组间(阳性率为0)并无明显差异(P>0.05);尿沉渣PTEN基因甲基化对膀胱癌诊断的敏感性为48.7%(19/39),特异性为91.5%(54/59)。性别、年龄、病理分级及临床分期与PTEN基因甲基化均无明显相关性(P均>0.05)。结论 PTEN基因启动子异因异常甲基化可能是膀胱癌的早期事件,尿沉渣PTEN基因启动子异常甲基化可能是膀胱癌早期诊断分子标志物之一。

Objective To evaluate promoter methylation of PTEN（Phosphates and Tension homolog deleted on chromosome Ten） gene and its clinical significance. Methods 39 Patients which clinically final diagnosis by pathology for bladder transitional cell cancer were included in this study. The methylation status of PTEN in cancer tissues and paired urine sediments was examined by MSP method. Results The frequence of methylation of PTEN gene in cancer tissues and paired urine sediments was 53.8% （21/39） , 48.7% （ 19/ 39 ） , respectively. There was a statistically significant relationship between them （ r = 0. 381, P = 0. 017 ）. The frequence of methylation of PTEN gene in urine sediments with bladder cancers was significantly higher than that in noncancerous urinary lesion patients（x2 = 15.37, P = 0. 000）. No hypermetylation of PTEN was observed in normal health individuals. No association between methylation status and grad- ing or staging was demonstrated（P 〉 0.05）. The sensitivity and specificity of aberrant methylation of PTEN gene in urine sediments for detecting bladder cancer was 48.7% （19/39） and 91.5% （54/59）. Conclusion Hypermethylation of PTEN in urine sediment DNA is a potential biomarker for detecting bladder cancer.