散发性大肠癌CpG岛甲基子表型的基因表达  

Genes expression profile of sporadic colorectal cancer with CpG island methylator phenotype

作　　者：蔡国响[1] 徐烨[1] 蔡三军[1] 师英强[1] 陆洪芬[2] 管祖庆[1] 廉朋[1] 彭俊杰[1] 周晓燕[2] 杜祥[2] 施达仁[2] 

机构地区：[1]复旦大学附属肿瘤医院腹部外科,上海200032 [2]复旦大学附属肿瘤医院病理科,上海200032

出　　处：《中华消化杂志》2007年第3期158-161,共4页Chinese Journal of Digestion

基　　金：本课题系上海市卫生局科技发展基金资助项目（024072）

摘　　要：目的探讨CpG岛甲基子表型阳性的散发性大肠癌的基因表达特征。方法对71例散发性大肠癌采用甲基化特异性PCR法行p14^ARF、人类mut-s同系物1（hMLH1）、p16^INK4a、6-氧-甲基鸟嘌呤-DNA甲基转移酶（MGMT）和肿瘤甲基化位点1（MINT1）共5个基因启动子甲基化的检测，确定CpG岛甲基子表型；进行K-ras、APC、P53、Bax和转化生长因子βⅡ受体（TGFβRⅡ）共5个基因的免疫组化检测。分析散发性大肠癌CpG岛甲基子表型和基因表达之间的关系。结果71例散发性大肠癌中，CpG岛甲基子表型阳性率为21．1％（15／71）；K-ras、APC、P53、Bax和TGFβRⅡ蛋白阳性表达率分别为43．7%（31／71）、42．3％（30／71）、47．9％（34／71）、71．4%（50／70）和59．2％（42／71）。CpG岛甲基子表型和APC、P53、Bax、TGFβRⅡ蛋白表达均无显著相关性，但与K-ras蛋白表达显著相关，CpG岛甲基子表型阳性者K—ras蛋白阳性表达率显著高于CpG岛甲基子表型阴性者（66．7%比37．5％，P=0．043）。结论CpG岛甲基子表型阳性的散发性大肠癌中K—ras蛋白呈高表达，提示多基因同时甲基化与K—ras蛋白的激活表达密切相关，两者的关系表明表遗传学机制可以间接引起遗传学改变。Objective To explore genes expression profile of sporadic colorectal cancer（SCRC） with CpG island methylator phenotyp（CIMP）. Methods Seventy one cases of SCRC were evaluated for CIMP by the promotor hypermethylation of p14^ARF , hMLH1, p16^INK4a , MGMT and MINT1 with methylation specific PCR. The protein expressions of K-ras, APC, P53, Bax and TGFβRⅡ were determined by immunohistochemistry. Results The positive rate of CIMP in SCRC was 21.1%（15/71）. The positive rates of protein expression of K-ras, APC, P53, Bax and TGFβRⅡ were 43.7%（31/71）, 42.3% （30/71）, 47.9%（34/71）, 71.4% （50/70） and 59.2% （42/71）, respectively. No significant correlation between CIMP and expression of APC, P53, Bax or TGFβRⅡ was found in the study. However, there was a significant correlation between CIMP and K-ras expression. The K-ras expression was much higher among CIMP positive SCRC than those CIMP negative SCRC（66.7% vs. 37.5% respectively, P = 0. 043）. Conclusions SCRCs showing positive CIMP have a relatively higher rate of activated K-ras protein expression compared with those CIMP negative. The close relation between CIMP and K-ras protein expression indicates that epigenetic mechanism could cause genetic changes indirectly.

关 键 词：结直肠肿瘤 CPG岛 甲基化 表型 

分 类 号：R686[医药卫生—骨科学]