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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 and adjacent non-tumorous tissues, and to investigate its mRNA and protein expression and Wnt pathway ectopic β-catenin The impact of expression. Methods: Methylation-specific PCR (MSP) was used to detect the methylation status of Caveolin-1 gene in 138 cases of gastric cardia adenocarcinoma and adjacent noncancerous tissues, and to further analyze the gene methylation And the clinicopathological features of the patients. The expression of Caveolin-1 mRNA in gastric cardia adenocarcinoma and adjacent noncancerous tissues was detected by RT-PCR. The expression of Caveolin-1 and beta-catenin protein were detected by immunohistochemistry The relationship between Caveolin-1 gene methylation, Caveolin-1 mRNA, protein expression and ectopic expression of β-catenin protein was further analyzed by Spearman’s rank correlation analysis. Results: The methylation rate of Caveolin-1 gene in gastric cardia adenocarcinoma was 26.1% (36/138), which was significantly higher than that in adjacent non-cancerous tissues (P <0.01). The high methylation level of Caveolin-1 (P <0.05), and had no correlation with clinical stage (P> 0.05). The expression of Caveolin-1 in cancer tissue was correlated with lymph node metastasis, family history of upper gastrointestinal cancers (UGIC) and tumor pathological grade 1 mRNA and protein were 48.6% and 32.6% respectively, which were significantly lower than those in adjacent non-tumorous tissues (P <0.01). The ectopic expression rates of β-catenin protein in cancer tissues and paracancerous tissues were 87.7% and 39.9%, respectively, with statistical significance (P <0.01). The ectopic expression of Caveolin-1 mRNA and its protein and β-catenin protein in cancerous tissues were significantly correlated with the methylation status of Caveolin-1 (P <0.05). Conclusion: CpG island methylation is one of the mechanisms of down-regulation of Caveolin-1 gene expression. The methylation of Caveolin-1 gene may play an important role in the occurrence of GCA by activating the Wnt / β-catenin signaling pathway.