多基因甲基化检测在尿路上皮癌中作用的研究  

The Role of Promoter Hypermethylation in Urothelial Carcinoma

作　　者：李振华[1] 高小林[1] 于秀月[1] 张哲[1] 李白[1] 孔垂泽[1] 

机构地区：[1]中国医科大学附属第一医院泌尿外科,沈阳110001

出　　处：《中国医科大学学报》2013年第7期648-652,共5页Journal of China Medical University

摘　　要：目的探讨多基因甲基化检测在尿路上皮癌诊断中的价值。方法应用甲基化特异性聚合酶链式反应检测36例膀胱尿路上皮癌和24例上尿路尿路上皮癌组织中GSTP1、APC、DKK-3、RASSF1A、DAPK、EDNRB、TNFRSF25、P16和MGMT共9种基因的甲基化状态。结果在尿路上皮癌组织中RASSF1A、DAPK、EDNRB、TNFRSF25和P16基因异常甲基化的程度相对比较高,分别是83.3%、75.0%、85.0%、70.0%和55.0%,而APC、DKK-3、GSTP1和MGMT基因异常甲基化的程度相对较低,分别是3.3%、25.0%、23.3%和5.0%。甲基化程度与病理分级和分期没有显著关系(P>0.05)。在上尿路尿路上皮癌中,RASSF1A、DAPK、EDNRB、TNFRSF25和P16基因的甲基化率分别是91.7%、95.8%、83.3%、70.8%和33.3%,而在膀胱尿路上皮癌中,RASSF1A、DAPK、EDNRB、TNFRSF25和P16基因的甲基化率分别是77.8%、61.1%、91.7%、69.4%和69.4%。结论在尿路上皮癌中RASSF1A、DAPK、EDNRB、TNFRSF25和P16基因甲基化过表达。DAPK和P16基因的甲基化检测可能有助于上尿路尿路上皮癌和膀胱尿路上皮癌的定位鉴别诊断。Objective To inveaigate the significance of the multi-gene DNA methylation status detection in the diagnosis of urothelial carcinoma. Methods The methylation status of 9 genes including GSTP1, APC, DKK-3, RASSFIA, DAPK, EDNRB, TNFRSb25, P16 and MGMT was analyzed by the method of methylation-specific polymerase chain reaction in 24 cases of upper urinary tract urothelial carcinoma and 36 cases of bladder urothelial carcinoma. Results In urothelial carcinomas tumor tissues, aberrant methylation was frequently detected in RASSF1 （83.3%）,DAPK （75.0%）,EDNRB （85.0%）,TNFRSF25 （70.0%）,and P16 （55.0%）,whereas the methylation off APC （3.3%）, DKK-3 （25.0%）, GSTP1 （23.3%）, MGMT （5.0%） was not common. There was no association between the tumor methylation status of these genes and the tumor grade or stage （P 〉 0.05）. In the upper urinary tract urothelial carcinomas, the methylation tale of RASSF1,DAPK,EDNRB, TNFRSF25,and P16 was 91.7%,95.8%,83.3%,70.8%,and 33.3%,respectively. In the bladder urotbehal carcinoma tissues,the methylation rate of the above mentioned five genes was 77.8%, 61.1% ,91.7% ,69.4%, and 69.4%, respectively. Conclusions There is a distinct methylation pattern in urothehal carcinoma with frequently methylated genes including RASSF1, DAPK, EDNRB, TNFRSF25,and P16. Detection of the methylation of DAPK and PI6 might be helpful in the differential diagnosis of the upper urinary tract urothelial carcinoma and the bladder carcinoma.

关 键 词：尿路上皮癌 基因 甲基化 

分 类 号：R737.1[医药卫生—肿瘤]