贲门腺癌中SFRP1、DKK3基因启动子区甲基化状态的联合分析  

Hypermethylation of SFRP1 and DKK3 promoters in gastric cardia adenocarcinoma

作　　者：郭艳丽[1] 王馥丽[1] 郭炜[1] 邝钢[1] 杨植彬[1] 董稚明[1] 

机构地区：[1]河北医科大学第四医院省肿瘤研究所病理研究室,石家庄050011

出　　处：《临床与实验病理学杂志》2010年第2期154-157,共4页Chinese Journal of Clinical and Experimental Pathology

基　　金：河北省医学科研重点课题计划项目(20090466);河北省科技厅科技攻关项目(052761163)

摘　　要：目的研究贲门腺癌(gastric cardia adenocarcinoma,GCA)中Wnt通路拮抗基因分泌型卷曲相关蛋白1(SFRP1)和DKK3(Dickkopf3)基因的甲基化状态,探讨其与贲门腺癌发生的关系。方法应用甲基化特异性PCR(MSP)法检测89例贲门腺癌及相应正常黏膜组织中SFRP1和DKK3基因的甲基化状态,并分析与临床病理参数间的关系。结果89例贲门腺癌组织中SFRP1和DKK3基因发生甲基化的分别有77例(86.5%)和16例(20.0%),而正常黏膜组织中仅有15例(13.9%)发生了SFRP1基因的甲基化,未发现有DKK3基因的甲基化现象,癌组织中两基因的甲基化率均明显高于正常黏膜组织(P<0.05);SFRP1基因的高甲基化与肿瘤组织的淋巴结转移相关,而与肿瘤的浸润深度、临床分期及病理分级无关,DKK3基因的甲基化与各临床病理指标均无关(P>0.05);联合分析SFRP1和DKK3基因,在贲门腺癌组织中两基因共同发生甲基化的有12例,其共同甲基化率与肿瘤的淋巴结转移及TNM分期相关(P<0.05)。结论贲门腺癌中SFRP1和DKK3基因的高甲基化状态可能是引起贲门腺癌发生的分子机制之一;SFRP1、DKK3基因甲基化的联合检测对于贲门腺癌的预后评估有一定的参考价值。Purpose To investigate the promoter methylation of SFRP1 and DKK3 genes in gastric cardia adenocarcinoma（GCA）.Methods MSP method was applied to examine the promoter methylation of SFRP1 and DKK3 genes in 89 samples of tumors and corresponding normal mucosa.Results 77（86.5%） and 16（20.0%） GCA tissues showed SFRP1 and DKK3 genes methylation in 89 samples of tumors,while 15 samples showed SFRP1 gene methylation and DKK3 gene methylation was not found in normal mucosa.The frequency of SFRP1 and DKK3 gene methylation in GCA was higher than that in normal mucosa（P0.01）.Furthermore,the frequency of SFRP1 gene methylation was correlated with lymphatic metastasis（P0.05）,but not with invasion depth,clinical stage and pathological classification;and the methylation frequency of DKK3 gene had no correlation with clinical pathological features.12 tumor tissues showed co-methylation of both SFRP1 and DKK3 genes and the co-methylation frequency was related with lymphatic metastasis and clinical stage when SFRP1 and DKK3 were simultaneously analyzed.Conclusion Hypermethylation of SFRP1 and DKK3 genes may be one of the mechanisms that contribute to the pathogenesis of GCA.Combined analysis of methylation status of SFRP1 and DKK3 genes may have definite values in estimating prognosis of patients with GCA.

关 键 词：贲门肿瘤 腺癌 甲基化 SFRP1基因 DKK3基因 

分 类 号：R735.2[医药卫生—肿瘤]