胃和结直肠腺癌患者血清RASSF1A基因启动子异常甲基化检测及其临床意义  

RASSF1A promoter hypermethylation of serum DNA in gastric and colorectal adenocarcinoma patients

作　　者：于正洪[1] 史兆荣[2] 高勇[3] 王玉才[1] 苏全胜[1] 郁红菊[1] 刘畅[1] 林勇[1] 马驰原[4] 

机构地区：[1]南京军区南京总医院肿瘤内科,南京210002 [2]南京军区南京总医院干部保健科,南京210002 [3]南京军区南京总医院普通外科,南京210002 [4]南京军区南京总医院博士后科研工作站,南京210002

出　　处：《癌症进展》2011年第5期555-560,554,共7页Oncology Progress

基　　金：江苏省六大人才高峰重点课题基金资助项目(批准号:2005A2);南京军区南京总医院科研课题(批准号:2009M033)

摘　　要：目的研究胃和结直肠腺癌患者血清RASSF1A基因启动子区域的甲基化状态及其临床意义。方法采用甲基化特异性聚合酶链反应(MSP)技术,检测47例胃腺癌患者、45例结直肠腺癌患者、60例胃肠道良性病变患者及30例健康志愿者血清RASSF1A基因启动子区域的甲基化状态,并同时检测25例进行手术的胃腺癌、结直肠腺癌患者的肿瘤组织和邻近正常组织的RASSF1A基因的甲基化状态,分析其与临床病理参数之间的相关性。结果 47例胃腺癌患者血清RASSF1A基因启动子区域异常甲基化16例,检出率为34.0%,45例结直肠腺癌患者血清RASSF1A基因启动子区域异常甲基化13例,检出率为28.9%,而30例胃部良性疾病患者的检出率为3.3%(1/30),30例结直肠良性疾病患者的检出率为6.7%(2/30),30例健康志愿者中检出率均为0(0/30),差异有统计学意义,均为P<0.01。25例进行手术的胃、结直肠腺癌患者血清中的RASSF1A启动子异常甲基化状态与之匹配的对应组织中的检出率是一致的,术前和术后血清中的基因甲基化检出率也是一致的。RASSF1A启动子异常甲基化与患者的性别、年龄、肿瘤分期、手术治疗和血清中的CEA水平无关。结论 RASSF1A启动子异常甲基化在胃和结直肠腺癌患者血清中有着较高的检出率,有望成为胃和结直肠腺癌诊断和预后的分子标志。Objective To detect the hypermethylation of RASSF1A promoter in serum DNA of the gastric and colorectal adenocarcinoma patients and to analyze its correlation with clinicopathological features. Methods Serum DNA was extracted from peripheral blood of 47 primary gastric adenocarcinoma patients, 45 primary colorectal adenocarcinoma patients, 60 benign gastrointestinal disease patients and 30 healthy donors. In 25 gastric and colorectal adenocarcinoma patients who later underwent surgical therapy, promoter methylation of RASSF1A was compared in primary tumor, adjacent normal tissue and postoperative serum. The methylation of RASSF1A promoter was determined by mthylation-specific PCR, and the correlation between methylation and clinicopathological parameters was statistically analyzed. Results The frequencies of RASSF1A promoter hypermethylation in gastric （34. 0% , 16/47） and colorectal （28.9% , 13/45） ade- noeareinoma patients were significantly higher than those of benign gastric （3. 3%, 1/30） and colorectal （6. 7% , 2/ 30） disease patients （P 〈 0. 001 ）. And no hypermethylation appeared in healthy donors. Hypermethylation of RASSF1A was consistent in serum samples and paired primary tumor, and RASSF1A promoter methyaltion level was consistent in paired pre-and postoperative serum samples. We also found that RASSF1A promoter hypermethylation was not associated with gender, age, tumor differentiation grade, surgical therapy or serum CEA level. Conclusion RASSF1A promoter is frequently hypermethylated in serum DNA of primary gastric and colorectal adenocarcinoma patients, and it may be a prom- ising novel biomarker for the diagnosis and prognosis of gastric and colorectal adenocarcinomas.

关 键 词：胃癌 结直肠癌 RASSF1A基因 DNA甲基化 

分 类 号：R735.2[医药卫生—肿瘤] R735.3[医药卫生—临床医学]