目的：检测贲门腺癌（gastric cardia adenocarcinoma，GCA）组织及相应癌旁非肿瘤组织中Y性别决定区基因7（sex determining region Y-box 7, SOX7 ）的甲基化状态及其对 SOX7 mRNA表达、Wnt通路中心因子β-catenin异质表达的影响及与临床病理特征之间的相关性。方法：选择河北医科大学第四医院胸外科2006-2012年手术切除的GCA及癌旁组织各130例，应用甲基化特异性PCR（methylation specific PCR, MSP）、RT-PCR分别检测130例GCA及癌旁组织中 SOX7 基因的甲基化状态及其mRNA表达情况，应用免疫组织化学方法检测标本中β-catenin蛋白的表达。分析 SOX7 的甲基化状态与临床病理特征、 SOX7 mRNA表达、β-catenin蛋白的异质表达及上消化道肿瘤家族史（upper gastrointestinal cancers，UGIC）的关系。 结果 ：GCA组织中 SOX7 的甲基化率显著高于癌旁组织为\[57.7%（75/130） vs 30.8%（40/130）， P <0.01\]，其高甲基化仅与肿瘤患者的淋巴结转移情况有关（ P <0.05），与肿瘤组织的病理分级及临床分期均无关（ P >0.05）。GCA组织中 SOX7 mRNA的表达量明显低于癌旁非肿瘤组织\[(0.414±0.054) vs (0.695±0.034)， P <0.01]\]，其β-catenin蛋白的异质表达率显著高于癌旁组织（85.4% vs 43.1%， P <0.01）；GCA组织中 SOX7 基因mRNA表达情况及β-catenin蛋白的异质表达率均与该基因的甲基化状态有关（ P <0.05），并且 SOX7 基因的甲基化状态与贲门癌患者的上消化道家族史密切相关（ P <0.01）。结论： CpG岛甲基化是 SOX7 基因表达下调的机制之一，并可能通过Wnt/β-catenin信号转导通路的激活在贲门腺癌的发生中扮演着重要的角色。

Objective:To determine the methylation status and expression of SOX7 gene in association with Wnt signaling and clinicopathological characteristics in gastric cardia adenocarcinoma (GCA). Methods: Paired specimens of primary tumor and corresponding adjacent tissues were collected from 130 patients who were diagnosed with GCA and underwent surgical ablation in the Thoracic Surgery, Fourth Hospital Affiliated to Hebei Medical University in Shijiazhuang between 2006 and 2012. Methylation of CpG sites within the SOX7 gene promoter was assessed by methylation specific PCR (MSP), SOX7 mRNA abundance by RT-PCR, and β-catenin protein by immunohistochemistry, in these speciments. Associations of the methylation status of the SOX7 gene promoter with SOX7 mRNA abundance, β-catenin protein contents, clinicopathologic variables and the history of the upper gastrointestinal cancers (UGIC), respectively, were assessed. Results: The frequency of SOX7 gene methylation was significantly higher in GCA tissue (57.7%) than that in the adjacent non-cancerous tissues ( P <0.01). The hypermethylation of this gene was correlated with lymph node metastasis ( P <0.05) but neither with pathological grade nor clinical stage ( P >0.05). SOX7 mRNA abundance was significantly lower in GCA tissue (0.414±0.054) than that in the corresponding adjacent tissues (0.695±0.034, P <0.01). The ectopic expression frequency of β-catenin was significantly different between GCA and adjacent tissue specimens (85.4% vs 43.1%, P <0.05). SOX7 mRNA and β-catenin protein levels were significantly correlated with the frequency of SOX7 gene methylation in GCA tissue ( P <0.05). In addition，the methylation status of the SOX7 gene was closely related with the history of UGIC ( P <0.01). Conclusion: Hypermethylation of CpG sites within the SOX7 gene promoter and the resultant aberration of canonical Wnt/β-catenin signaling may play an important role in the pathogenesis of GCA.

河北省自然科学基金资助项目（No. H2013206315）；河北省医学科研重点课题计划项目（No. 20130543）