贲门腺癌中Caveolin-1基因的甲基化状态及其与β-catenin异位表达的关系  

Methylation status of Caveolin-1 gene and its relationship with ectopic expression of β-catenin in gastric cardia adenocarcinoma

作　　者：郭艳丽[1] 周珍[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/河北省肿瘤研究所病理研究室,河北石家庄050011

出　　处：《肿瘤》2014年第9期825-830,共6页Tumor

基　　金：河北省自然科学基金资助项目(编号:H2013206315)

摘　　要：目的 :检测贲门腺癌及相应癌旁非肿瘤组织中Wnt通路相关因子Caveolin-1基因的甲基化状态,探讨该基因甲基化对其mRNA、蛋白表达及Wnt通路中心因子β-catenin异位表达的影响。方法 :采用甲基化特异性PCR(methylation-specii c PCR,MSP)法检测138例贲门腺癌及相应癌旁非肿瘤组织中Caveolin-1基因的甲基化状态,并进一步分析基因甲基化与患者临床病理特征之间的关系;采用RT-PCR法检测贲门腺癌及相应癌旁非肿瘤组织中Caveolin-1 mRNA表达情况,应用免疫组织化学法检测Caveolin-1及β-catenin蛋白的表达情况,并进一步应用Spearman等级相关分析法分析Caveolin-1基因甲基化与Caveolin-1 mRNA、蛋白表达以及β-catenin蛋白异位表达的相关性。结果 :在贲门腺癌组织中,Caveolin-1基因的甲基化率为26.1%(36/138),明显高于癌旁非肿瘤组织(P<0.01);癌组织中Caveolin-1基因的高甲基化与肿瘤患者的淋巴结转移、上消化管肿瘤(upper gastrointestinal cancers,UGIC)家族史以及肿瘤组织的病理分级有关(P<0.05),而与临床分期无关(P>0.05);癌组织中Caveolin-1 mRNA及蛋白的阳性表达率分别为48.6%和32.6%,均明显低于癌旁非肿瘤组织(P<0.01)。癌及癌旁组织中β-catenin蛋白的异位表达率分别为87.7%和39.9%,差异有统计学意义(P<0.01)。癌组织中Caveolin-1 mRNA及其蛋白表达和β-catenin蛋白的异位表达均与Caveolin-1基因的甲基化状态明显相关(P<0.05)。结论 :CpG岛甲基化是Caveolin-1基因表达下调的机制之一。Caveolin-1基因甲基化可能通过激活Wnt/β-catenin信号转导通路,在贲门腺癌的发生中发挥着重要的作用。Objective： To detect the methylation status of Wnt pathway-related factor Caveolin-1 gene in gastric cardia adenocarcinoma （GCA） and adjacent non-cancerous tissues, and to explore the impact ofCaveolin-1 gene methylation on the expressions of its mRNA and protein and β-catenin, a central factor of Wnt pathway. Methods： The methylation status of Caveolin-1 gene in GCA and the corresponding adjacent non-cancerous tissues from 138 patients was detected by methylation-specific PCR （MSP）, and the relationship of methylation status of this gene with the clinicopathological features of GCA patients was analyzed. The expressions of Caveolin-1 mRNA in GCA and the corresponding adjacent non-cancerous tissues were detected by reverse transcription-PCR （RT-PCR）. The expressions of Caveolin-1 protein and β-catenin were detected by immunohistochemistry. The correlations of methylation status of Caveolin-1 gene with the expressions of Caveolin-1 mRNA and protein and the ectopic expression of β-catenin protein were further analyzed by Spearman rank correlation test. Results： In the GCA tissues, the frequency of Caveolin-1 gene methylation was 26.1% （36/138）, which was significantly higher than that in the corresponding adjacent non-cancerous tissues （P 〈 0.01）. The hypermethylation of Caveolin-1 gene was correlated with lymph node metastasis, family history of upper gastrointestinal cancer and pathological grade （all P 〈 0.05）, but not correlated with clinical stage （P 〉 0.05）. The positive-expression rates of Caveolin-1 mRNA and protein were 48.6% and 32.6%, respectively, which were both lower than those in the corresponding adjacent non-cancerous tissues （P 〈 0.01）. The ectopic expression frequencies of β-catenin protein were 87.7% and 39.9% in GCA and the corresponding adjacent non-cancerous tissues, respectively; there was a significant difference between the two groups （P 〈 0.01）. The expressions of Caveolin-1 mRNA and protein and the ectopic expression of β-catenin p

关 键 词：胃肿瘤 贲门 窖蛋白1 DNA甲基化 基因表达 Β连环素 

分 类 号：R735.2[医药卫生—肿瘤]