膀胱癌尿沉渣RUNX3基因启动子区域CpG岛甲基化状况及意义

Detection of Promoter Methylated RUNX3 Gene in Urine Sediments in Patients with Bladder Cancer

目的探讨膀胱癌患者尿沉渣细胞中RUNX3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RUNX3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RUNX3基因启动子甲基化阳性率分别为64.1%(25/39)和56.4%(22/39),二者密切相关(r=0.420,P=0.008)。膀胱癌组尿沉渣RUNX3基因启动子甲基化阳性率(64.1%,25/39)显著高于非肿瘤组(6.7%,3/45)(χ2=31.015,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RUNX3基因甲基化对膀胱癌诊断的敏感性为64.1%(25/39),特异性为94.9%(56/59)。浸润性(≥pT2)和表浅性(≤pT1)膀胱癌RUNX3基因甲基化阳性率之间的差异有统计学意义(χ2=10.363,P=0.001)。性别、年龄、病理分级与RUNX3基因甲基化均无明显相关性(均P>0.05)。结论 RUNX3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RUNX3基因启动子异常甲基化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 RUNX3 gene and its clinical significance. Methods Totally 39 patients which were diagnosed by pathology for bladder transitional cell cancer were included in this study. The methylation status of RUNX3 in cancer tissues and paired urine sediments was examined by MSP method. Results The frequenee of methylation of RUNX3 gene in cancer tissues and paired urine sediments was 64.1% （25/39） , 56.4% （22/39） , respectively. There was a statistically significant relationship between them （r = 0. 420,P = 0. 008）. The frequence of methylation of RUNX3 gene in urine sediments with bladder cancers was significantly higher than that in noncancerous urinary lesion patients （X2 = 31. 015, P = 0. 000）. No hypermetylation of RUNX3 was observed in normal health individuals. RUNX3 methylation correlated significantly with invasive bladder tumors compared to superficial tumors. No association between methylation status and gender, aging or tumor grade was demonstrated（P 〉 0.05 ）. The sensitivity and specificity of aberrant methylation of RUNX3 gene in urine sediments for detecting bladder cancer was 64.1% （25/39） and 94.9% （56/ 59）. Conclusion Hypermethylation of RUNX3 in urine sediment DNA could be a promising marker for bladder cancer diagnosis and prognosis prediction.