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CpG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) gene in gastric cardia adenocarcinoma (GCA) tissues and adjacent non-cancerous tissues, and to study its clinical significance. Methods: Methylation specific PCR (MSP) and quantitative RT-PCR were respectively applied to examine the CpG methylation of the DACT-1 gene and expression of its mRNA in tumor tissues and corresponding adjacent noncancerous tissues of 112 samples (collected from Department of Surgery, the Fourth Hospital Affiliated to Hebei Medical University and Department of Thoracic Surgery, Cixian Cancer Hospital during 2006 to 2014). Results: Methylation rates of DACT-1 gene in the GCA tissues and the adjacent noncancerous tissues were 51.8% (58/112) and 17.6% (20/112) respectively, indicating that methylation rate of DACT-1 in the GCA tissues was significantly higher than that in the noncancerous tissues (P<0.01). Expression of DACT-1 mRNA in the cancer tissues was 0.580±0.143, which was significantly lower than that in the adjacent noncancerous tissues (0.654±0.110，P<0.01). Expression of DACT-1 mRNA in the GCA tissues with methylated DACT-1 was 0.488±0.097, which was obviously lower than that in the GCA tissues with unmetylated ACT-1 (0.675±0.120), and the methylation status of the gene was significantly related with expression of its mRNA（P<0.01). The hypermethylation of DACT-1 gene in the GCA tissues was significantly related with lymph node metastasis and family history of upper gastrointestinal cancer (P<0.05), but not related with age, gender, pathological grading and clinical staging of the cancer patients（P>0.05）. Conclusion: The hypermethylation of CpG in DACT-1 3gene might be one of the mechanisms causing down-regulation of DACT-1 expression. The methylation status of promoter area in DACT-1 gene is expected to provide a novel indicator for the clinical diagnosis and prognosis evaluation of GCA.

河北自然科学基金资助项目（No. H2013206315）；河北省医学科学研究重点课题计划项目(No,20130543）