食管胃交界癌前病变及早期癌组织HINT1基因甲基化状态分析  

Analysis of methylation status of HINT1 gene in precancerous lesions and early cancer of esophagogastric junction

作　　者：袁丽[1] 曹玉[2] 杨惠珍 张立玮[1] 郭硕[1] 徐志彬[1] 尔丽绵[1] YUAN Li;CAO Yu;YANG Hui-zhen;ZHANG Li-wei;GUO Shuo;XU Zhi-bin;ER Li-mian(Fourth Hospital of Hebei Medical University,Shijiazhuang 050011,P.R.China;Endoscopy Room of Jiaozuo Second People’s Hospital,Jiaozuo 454000,P.R.China)

机构地区：[1]河北医科大学第四医院内镜室,河北石家庄050011 [2]河北医科大学第四医院河北省癌症早诊早治项目办公室,河北石家庄050011 [3]河南省焦作市第二人民医院内镜室,河南焦作454000

出　　处：《中华肿瘤防治杂志》2019年第21期1606-1610,共5页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家重点研发计划（2016YFC1302800;2016YFC0901400）;河北省医学科学研究重点课题（20160661）

摘　　要：目的组氨酸三聚体核苷结合蛋白1基因具有明显的肿瘤抑制作用,本研究旨在探讨食管胃交界癌前病变及早期癌中HINT1启动子区CpG岛甲基化状态及临床意义。方法提取2012-2-1-2013-12-30河北医科大学第四医院诊治的食管胃交界癌前病变、早期癌及进展期癌共184例病变组织及45例正常对照组织基因组DNA。根据Siewert分型分为TypeⅠ型、TypeⅡ型和TypeⅢ型。TypeⅠ型包括Barrett食管31例(BE组)、食管远端高级别上皮内瘤变及早期癌16例(EHIN及EEC组)、食管腺癌18例(EA组);TypeⅡ型包括贲门低级别上皮内瘤变23例(CLIN组)、贲门高级别上皮内瘤变及早期癌30例(CHIN及CEC组),贲门腺癌36例(CA组);TypeⅢ型包括近端胃低级别上皮内瘤变14例(SGLIN组)、近端胃高级别上皮内瘤变及早期癌12例(SGHIN及SGEC组),近端胃癌4例(SGA组)。采用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)检测上述组织中HINT1基因启动子区CpG岛甲基化状态,对比分析HINT1基因甲基化与食管胃交界不同癌变阶段的相关性。结果 (1)TypeⅠ型:BE组、EHIN及EEC组、EA组和对照组甲基化发生率分别为12.9%(4/31)、43.8%(7/16)、50.0%(9/18)和0,EHIN及EEC组HINT1基因甲基化率显著高于对照组(χ~2=6.64,P=0.007)和BE组(χ~2=5.601,P=0.029),与EA组比较差异无统计学意义(χ~2=0.133,P=0.716)。(2)TypeⅡ型:CLIN组、CHIN及CEC组、CA组和对照组甲基化率分别为34.8%(8/23)、53.3%(16/30)、55.6%(20/36)和6.7%(1/15),CHIN及CEC组和CA组HINT1基因甲基化率显著高于对照组(χ~2=9.265,P=0.002),CHIN及CEC组、CA组和CLIN组比较差异无统计学意义(χ~2=2.697,P=0.260)。(3)TypeⅢ型:SGLIN组、SGHIN及SGEC组、SGA组和对照组甲基化率分别为21.4%(3/14)、66.7%(8/12)、75.0%(3/4)和6.7%(1/15),SGHIN及SGEC组与对照组(χ~2=10.80,P=0.003)和SGLIN组(χ~2=5.418,P=0.045)比较差异均有统计学意义。结论 HINT1基因启动子区异常甲基化可能与食管胃�OBJECTIVE The gene of histidine triad nucleotide-binding protein1 has a significant tumor inhibition effect.The purpose of this study was to investigate the methylation status and clinical significance of CpG island of the promoter region of HINT1 in precancerous lesions of the esophagogastric junction and early cancers.METHODS FromFebruary 1,2012 to December 30,2013,the genomic DNA was extracted from 184 cases of precancerous lesions,early cancers and advanced cancers of esophagogastric junction and 45 cases of normal control diagnosed in the Fourth Hospital of Hebei Medical University.According to Siewert classification,type Ⅰ included Barrett esophagus(BE)31 cases,distal esophageal high-grade intraepithelial neoplasia or early carcinoma(EHIN and EEC)16 cases,esophageal adenocarcinoma(EA)18 cases;TypeⅡincluded cardiac low level intraepithelial neoplasia(CLIN group)23 cases,cardiac highgrade intraepithelial neoplasia or early carcinoma(CHIN and CEC)30 cases,cardia adenocarcinoma(CA)36 cases;TypeⅢincluded proximal stomach low level intraepithelial neoplasia(SGLIN)14 cases,proximal stomach high-grade intraepithelial neoplasia or early carcinoma(SGHIN and SGEC)12 cases,proximal gastric cancer(SGA)4 cases.Methylation specific polymerase chain reaction(MSP)was used to detect the methylation status of CpG island in the promoter region of HINT1 gene in the above tissues,and the correlation between methylation of HINT1 gene and different stages of esophageal and gastric junction cancer was analyzed.RESULTS (1)TypeⅠ:The methylation rates in BE,EHIN and EEC,EA and the control group were 12.9%(4/31),43.8%(7/16),50.0%(9/18)and 0,respectively.HINT1 gene methylation rate in EHIN and EEC group was significantly higher than those in the control group(χ~2=6.64,P=0.007)and BE group(χ~2=5.601,P=0.029).There was no statistically significant difference in comparison with the EA group(χ~2=0.133,P=0.716).(2)TypeⅡ:The methylation rates in the CLIN,CHIN and CEC,CA,and the control group were34.8%(8/23),53.3%(16/30),55.6%(20/

关 键 词：食管胃交界 HINT1基因 MSP 早期癌 癌前病变 

分 类 号：R73[医药卫生—肿瘤]