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目的:检测贲门腺癌(gastric cardia adenocarcinoma,GCA)及相应癌旁非肿瘤组织中β-环连蛋白抑制基因1(dishevelled-binding antagonist of beta-catenin 1,DACT-1)的甲基化状态,并探讨其临床意义。方法:应用甲基化特异性PCR(methylation specific PCR,MSP)、定量RT-PCR的方法分别检测112例贲门腺癌(河北医科大学第四医院外科和磁县肿瘤医院胸外科于2006-2014年收治)及相应癌旁非肿瘤组织中DACT-1基因的甲基化状态及其mRNA表达情况。结果:在贲门腺癌组织中,DACT-1基因的甲基化率为51.8%(58/112),癌旁非肿瘤组织中该基因的甲基化率为17.6%(20/112),癌组织中DACT-1基因发生甲基化的频率明显高于癌旁非肿瘤组织(P<0.01);癌组织中DACT-1基因mRNA的表达量为0.580±0.143,明显低于癌旁非肿瘤组织(0.654±0.110,P<0.01);在DACT-1基因甲基化的贲门癌组织中该基因mRNA的表达量为0.488±0.097,明显低于该基因未甲基化的贲门癌组织(0.675±0.120),且该基因甲基化状态与其mRNA表达量相关(P<0.01)。癌组织中DACT-1基因的高甲基化状态与肿瘤患者的淋巴结转移情况及上消化道肿瘤家族史有关(P<0.05),而与肿瘤患者的年龄、性别及肿瘤组织的病理分级、临床分期均无关(P>0.05)。结论:贲门腺癌中基因Cp G岛的高甲基化可能是DACT-1基因表达下调的机制之一;DACT-1基因启动子区的甲基化状态有望为贲门腺癌临床辅助诊断和预后评估提供新的指标。
Objective: To detect the methylation status of dishevelled-binding antagonist of beta-catenin 1 (DACT-1) in gastric cardia adenocarcinoma (GCA) And explore its clinical significance. Methods: A total of 112 patients with cardia adenocarcinoma were studied by methylation specific PCR (MSP) and quantitative RT-PCR (Department of Thoracic Surgery, Fourth Hospital of Hebei Medical University and Department of Thoracic Surgery, Cixian Cancer Hospital in 2006-2014 And the corresponding non-cancerous adjacent tissue DACT-1 gene methylation status and mRNA expression. RESULTS: The methylation rate of DACT-1 gene in gastric cardia adenocarcinoma was 51.8% (58/112). The methylation rate of this gene was 17.6% (20/112) in non-cancerous adjacent tissues. The frequency of methylation of DACT-1 gene was significantly higher than that in non-cancerous adjacent tissues (P <0.01). The expression of DACT-1 mRNA in cancer tissues was 0.580 ± 0.143, which was significantly lower than that in adjacent non-tumor tissues (0.654 ± 0.110, P <0.01). The mRNA expression level of methylated cardia carcinoma in DACT-1 gene was 0.488 ± 0.097, which was significantly lower than that in unmethylated gastric cardia carcinoma (0.675 ± 0.120), and the methylation status of the gene correlated with its mRNA expression (P <0.01). The hypermethylation status of DACT-1 gene in cancer tissues was related to the lymph node metastasis and the family history of upper gastrointestinal cancer (P <0.05), but not to the age, sex, tumor pathological grade and clinical stage Not related (P> 0.05). Conclusion: The hypermethylation of CpG island in gastric cardia adenocarcinoma may be one of the mechanisms of down-regulation of DACT-1 gene expression. The methylation status of DACT-1 gene promoter is expected to provide clinical assistant diagnosis and prognostic evaluation for cardiac adenocarcinoma New indicator