胃腺癌凝血栓蛋白1基因异常甲基化及其临床意义  

Aberrant methylation of CpG islands in thrombospondin 1 gene and its clinical significance in gastric adenocarcinoma

作　　者：张友才[1] 邓长生[1] 朱尤庆[1] 周燕[1] 

机构地区：[1]武汉大学中南医院消化内科,430071

出　　处：《中华消化杂志》2004年第8期455-458,共4页Chinese Journal of Digestion

基　　金：湖北省科技攻关计划课题 ( 2 0 0 2AA3 0 1C84)

摘　　要：目的　探讨凝血栓蛋白 1(THBS1)基因CpG岛异常甲基化与胃腺癌 (GAC)发生的关联。方法　应用甲基化特异性PCR检测技术 ,检测 82例GAC患者肿瘤组织 ,30例十二指肠球部溃疡 (对照组 )、30例慢性胃炎伴肠上皮化生或异型增生患者胃窦黏膜组织中 ,THBS1基因启动子CpG岛甲基化分布情况。结果　THBS1基因启动子CpG岛甲基化在对照组 (6 .7% )中的频率明显低于胃炎组(2 6 .7% ,χ2 =4 .32 ,P =0 .0 38)和胃癌组 (4 7.6 % ,χ2 =16 .2 ,P <0 .0 0 1) ,在胃炎组与胃癌组之间的频率差异也有显著性 (χ2 =4 .14 ,P =0 .0 4 2 ) ,老年胃癌患者 (6 3.6 % )中的频率明显高于非老年 (36 .7% ,χ2 =5 .72 ,P =0 .0 17) ,在TNMⅢ和Ⅳ期肿瘤 (6 6 .7% )组织中的频率明显高于Ⅰ期 (36 .8% )或Ⅱ期(36 .4 % ,χ2 =6 .93,v =2 ,P =0 .0 31) ,而肿瘤部位之间、Lauren分型肿瘤之间及不同分化程度肿瘤之间 ,THBS1基因甲基化率的差异无显著性。结论　THBS1基因启动子CpG岛甲基化可能与胃腺癌的发生有关 ,且以老年患者及Ⅲ和Ⅳ期肿瘤多见。Objective To study the relationship between aberrant methylation of CpG islands in thrombospondin (THBS) 1 and the pathogenesis of gastric adenocarcinoma (GAC). Methods Using methylation-special PCR (MSP), the methylation status of CpG islands for THBS1 of 82 GAC and 30 duodenal ulcer (control group) and 30 chronic gastritis with intestinal metaplasia or dysplasia were studied. Results The frequency for methylation of CpG island in THBS1 gene in control group (6.7%) was lower than that in chronic gastritis group (26.7%, χ2=4.32, P=0.038) and in GAC group (47.6%, χ2=16.2, P< 0.001), and there was statistic significances in frequency of CpG island methylation in THBS1 gene between chronic gastritis group and GAC group (χ2=4.14, P=0.042). The methylation of CpG island in THBS1 gene was significantly higher in elder GAC (63.6%) when compared with younger GAC (36.7%, χ2=5.72, P=0.017), and higher in patients of TNM Ⅲ and Ⅳ stages (66.7%) when compared with patients ofⅠ(36.8%) or Ⅱ stages ( 36.4%,χ2=6.93, v=2, P=0.031). There is no statistic difference in frequency of methylation of CpG island in THBS1 gene in different grade, site or Lauren type of GAC. Conclusion A aberrant methylation of CpG islands in THBS1 gene may play some roles in the pathogenesis of GAC, especially in the elder patients and later stage of GAC.

关 键 词：胃腺癌 凝血栓蛋白1 THBS1 基因异常 甲基化 CPG岛 肿瘤 

分 类 号：R735.2[医药卫生—肿瘤]