贲门腺癌组织中RASSF1A基因甲基化及其蛋白表达的研究  

Promoter hypermethylation and protein expression of RASSF1A gene in gastric cardia carcinoma

作　　者：樊宇靖[1] 刘宾[2] 王立东 蓝宇[1] FAN Yu -jing;LIU Bin;WANG Li - dong;et al.(Department of Gastroenterology, Beijing Jishuitan Hospital, Beijing 100035, China;Beijing Tongren Hospital Affiliated to Capital Medical University, Beijing 100730, China;Henan Key Laboratory for Esophageal Cancer Research, Zhengzhou Henan 450052, China)

机构地区：[1]北京积水潭医院消化内科,北京100035 [2]首都医科大学附属北京同仁医院消化内科,北京100730 [3]河南省食管癌重点开放试验室,河南郑州450052

出　　处：《临床和实验医学杂志》2018年第12期1250-1253,共4页Journal of Clinical and Experimental Medicine

基　　金：国家自然科学基金资助面上项目(编号:30670956)

摘　　要：目的探讨RASSF1A基因甲基化及其蛋白表达与贲门腺癌的相关性。方法回顾性将33例贲门腺癌手术切除标本纳入本研究,每例标本选取癌组织,癌旁正常组织(距癌>5 cm)组织各一块。采用甲基化特异性PCR检测RASSF1A基因的甲基化情况,采用免疫组织化学检测RASSF1A蛋白表达。结果 33例大体标本中共选取57块组织,其中癌组织33块,癌旁正常组织24块。贲门腺癌癌组织中RASSF1A基因甲基化的发生率为63.6%,明显高于贲门腺癌癌旁正常组织中RASSF1A基因甲基化的发生率(4.2%),两组比较差异有统计学意义(P<0.05)。贲门腺癌癌组织中RASSF1A蛋白阳性表达率为45.5%,明显低于贲门腺癌癌旁正常组织中RASSF1A蛋白阳性表达率(87.5%),两组比较差异有统计学意义(P<0.01)。21例RASSF1A基因甲基化阳性贲门癌组织中,15例(71.4%)蛋白表达阴性;12例RASSF1A基因甲基化阴性贲门癌组织中,9例(75%)蛋白表达阳性,3例(25%)蛋白表达阴性;经Spearman correlations相关分析发现:在贲门腺癌癌组织中RASSF1A基因甲基化与蛋白表达呈显著负相关(P<0.01)。结论RASSF1A基因可能通过启动子区甲基化导致的表达失活参与了贲门腺癌的发生发展过程。Objective To characterize the RASSF1A gene promoter hypermethylation and protein expression in gastric cardia adenocarcinoma（ GCA）. Methods Thirty-three GCA patients were enrolled from Yaocun Esophageal Cancer Hospital and Linzhou City Center Hospital.Surgically resected specimens were soon stored in the liquid nitrogen and then transferred to-80℃ refrigerator. Cancer tissue and paired normal tissue were selected in each patient. Methylation-specific polymerase chain reaction（ MSP） was used to investigate the methylation changes. Immunohisto-chemistry was used to detect protein expression. Results For GCA patients,RASSF1A promotor methylation frequency in cancer tissue and paired normal tissue was 63. 6%,4. 2%,respectively. RASSF1A positive protein expression in tumor tissue and paired normal tissue was45. 5%,87. 5%,respectively. In 21 cases of RASSF1A gene methylation（ ＋） cardiac cancer tissues,15 cases（ 71. 4%） had negative protein expression; in 12 cases of RASSF1A gene methylation（-） cardiac cancer tissues,9 cases（ 75%） were positive for protein expression. 3 cases（ 25%） were negative for protein expression. Spearman correlations correlation analysis found that there was negative correlations between promotor methylation and expression in RASSF1A（ P〈0. 01）. Conclusion Promotor hypermethylation of RASSF1A may be an analogous molecular event in GCA. RASSF1A may be a potential candidate biomarker for clinic early-detection.

关 键 词：贲门腺癌 RASSF1A基因 甲基化 

分 类 号：R735.2[医药卫生—肿瘤]