大肠癌患者血清中p16基因启动子畸变甲基化的检测  

Detection of aberrant p16 methylation in the serum of colorectal cancer patients

作　　者：邹鸿志[1] 郁宝铭[1] 赵任[1] 王志伟[2] 仓辉[2] 李东华[1] 冯国光[1] 易静[2] 

机构地区：[1]上海第二医科大学附属瑞金医院普外科,200025 [2]上海第二医科大学细胞生物学教研室

出　　处：《中华外科杂志》2002年第7期499-501,共3页Chinese Journal of Surgery

基　　金：卫生部科学研究基金 (98-1 3 0 3 );上海市高等学校科学技术发展基金 (2 0 0 0B0 2 )

摘　　要：目的　检测大肠癌患者血清DNA中p16基因启动子畸变甲基化 ,并探讨将它用于大肠癌早期诊断或作为一个预后因子的可能性。　方法　收集新鲜的大肠癌组织及其对应的血清标本5 2例 ,大肠腺瘤患者血清标本 34例 ,健康志愿者血清标本 10例。采用甲基化特异的PCR技术分别检测肿瘤组织DNA和血清游离DNA中p16基因启动子畸变甲基化的状况。分析血清中p16基因畸变甲基化与大肠癌临床病理特征的关系。　结果　 38% (2 0 / 5 2 )大肠癌组织出现p16高甲基化 ;与出现了高甲基化的组织标本对应的 2 0例血清标本中有 14例 (70 % )出现高甲基化 ,而其余 32例血清标本无一例检出高甲基化 (χ2 =30 7,P <0 0 1) ;34例大肠腺瘤患者和 10例健康志愿者的血清DNA中均未见p16高甲基化。血清p16基因高甲基化与大肠癌Dukes分期关系密切 (χ2 =5 7,P =0 0 3) ,但是与其它临床病理特征无关。　结论　大肠癌患者血清DNA中存在一定比例的p16基因启动子高甲基化。检测血清中p16基因的甲基化状况可能有助于大肠癌的早期发现或预后评估。Objectives To detect aberrant p16 promoter methylation in serum of patients with colorectal cancer(CRC), and to explore the possibility of using this assay in early detection or as a prognostic marker. Methods Methylation specific PCR was used to detect p16 methylation in DNA extracted from 52 CRCs and corresponding serum samples. Serum samples from 34 patients with adenomatous polyps and 10 healthy individuals were used as controls. The association of p16 hypermethylation in serum DNA of CRC patients with clinicopathological characteristics was analyzed. Results p16 methylation was found in 38%(20 of 52) of CRC tissues. Among the 20 patients with aberrant methylation in the tumor tissues, similar changes were also detected in the serum of 14 (70%) patients. No methylated p16 sequences were detected in the peripheral serum of the 32 CRC patients without these changes in the tumor, in 34 paitents with adenomatous polyps, or in 10 healthy controls. Clinicopathological analysis revealed that p16 methylation in serum was significantly associated with later Dukes′ stage (χ 2=5 7, P =0 03). Conclusion This assay offers a potential means for the serum based detection and/or monitoring of CRC patients.

关 键 词：大肠癌 P16基因 启动子畸变 甲基化 检测 

分 类 号：R735.34[医药卫生—肿瘤]