胃癌中DAPK基因启动子区CpG岛高甲基化的研究  

Study on methylation of CpG island in the promoter region of DAPK gene in gastric cancer

作　　者：孔祥勇[1] 胡世莲[1] 孙玉蓓[2] 沈干[3] 徐维平[4] 徐修才[5] 姜晓东[1] 黄大兵[1] 程昭栋[1] 

机构地区：[1]安徽医科大学附属省立医院老年医学科,合肥230001 [2]安徽医科大学附属省立医院肿瘤内科,合肥230001 [3]安徽省委机关医院干部病房,合肥230001 [4]安徽省循证医学中心,合肥230001 [5]安徽医科大学附属省立医院中心实验室,合肥230001

出　　处：《肿瘤》2009年第11期1065-1069,共5页Tumor

基　　金：国家自然科学基金资助项目(编号:30672383)

摘　　要：目的:探讨死亡相关蛋白激酶(death-associated protein kinase,DAPK)基因高甲基化与胃癌的发生以及临床病理特征之间的联系。方法:采用甲基化特异性聚合酶链反应(methylation-specific PCR,MSP)法分别检测66例胃癌患者的肿瘤组织、癌旁正常组织、手术前外周血浆以及37例术后血浆中DAPK基因启动子的甲基化状况,以20例健康人的外周血浆和胃镜活检正常胃组织作为对照。结果:胃癌组织中有66.7%(44/66)存在DAPK基因的异常甲基化,显著高于相应的癌旁正常组织[10.6%(7/66)],差异有统计学意义(P<0.001)。术前外周血浆中DAPK基因甲基化阳性率为16.7%(11/66);37例同时有胃癌根治术前后血浆标本的患者中,5例术前血浆甲基化阳性,术后全部转阴。而20例健康人的外周血浆和胃镜活检组织中均未检测到该基因甲基化。结论:DAPK基因在胃癌患者肿瘤组织和外周血浆中的高甲基化可能为胃癌的诊断以及临床预后评估提供有益的线索,手术后血浆中DAPK甲基化状态的变化可能与手术治疗有关。Objective ： To analyze the relationship between aberrant CpG island methylation of the death-associated protein kinase （DAPK） gene and tumorigenesis and clinicopathological parameters of human gastric cancer. Methods： Methylation-specific polymerase chain reaction （MSP） was used to detect promoter methylation status of the DAPK gene in 66 gastric cancer tissues and corresponding adjacent normal tissues and pre-operative plasma samples and 37 post-operative plasma samples. The plasma and normal gastric biopsy samples of 20 healthy subjects were collected as control. Results：Totally 66 patients were tested in this study, and the aberrant DAPK gene methylation was detected in 44 （66.7%） tumor tissues, which was significantly higher than that in adjacent normal tissues （7/66, 10.6% ,P 〈 0. 001 ）. The positivity of DAPK gene methylation pre-operative plasma was 16.7% （11/66）. For 37 patients who had pre- and post-operative plasma samples, DAPK gene had positive methylation in 5 pre-operalive plasma samples and it returned to nega- tive after radical surgery. However, no aberrant methylation was found in plasma and normal gastric biopsy samples of 20 healthy sub- jects. Conclusion：Promoter hypermethylation of the DAPK gene may provide useful information for the diagnosis and prediction of the prognosis in clinic. The alteration of methylation status of DAPK in post-operative plasma is related with surgical intervention.

关 键 词：胃肿瘤 DNA甲基化 钙-钙调素依赖性蛋白激酶 DAPK基因 血浆 

分 类 号：R735.2[医药卫生—肿瘤]