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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SOX7mRNA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:Cp G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 detect the methylation status of SOX7 in gastric cardia adenocarcinoma (GCA) tissues and its adjacent non-tumorous tissues and its effect on the expression of SOX7 mRNA , Wnt pathway center factor β-catenin heterogeneity and its relationship with clinicopathological features. Methods: 130 cases of GCA and adjacent non-cancerous tissues were selected from Department of Thoracic Surgery, the Fourth Hospital of Hebei Medical University from 2006 to 2012. 130 cases of GCA were detected by methylation-specific PCR (MSP) and RT-PCR And the methylation status of SOX7 gene and its mRNA expression in adjacent tissues. The expression of β-catenin in specimens was detected by immunohistochemistry. The relationship between the methylation status of SOX7 and clinicopathological characteristics, SOX7 mRNA expression, heterogeneous expression of β-catenin protein and upper gastrointestinal cancers (UGIC) was analyzed. Results: The methylation rate of SOX7 in GCA tissues was significantly higher than that in adjacent tissues [57.7% (75/130) vs 30.8% (40/130), P <0.01], and hypermethylation was only associated with lymph node metastasis (P <0.05), but not with the pathological grade and clinical stage (P> 0.05). The expression of SOX7 mRNA in GCA tissues was significantly lower than that in adjacent non-tumor tissues [(0.414 ± 0.054) vs (0.695 ± 0.034), P <0.01]. The heterogeneous expression of β-catenin protein in GCA tissues was significantly higher than that in paracancerous tissues (85.4% vs 43.1%, P <0.01). The mRNA expression of SOX7 and the heterogeneous expression of β-catenin in GCA tissues were correlated with the methylation status of SOX7 gene (P <0.05) The methylation status is closely related to the family history of upper gastrointestinal tract in patients with cardia cancer (P <0.01). CONCLUSION: CpG island methylation is one of the mechanisms of down-regulation of SOX7 gene expression and may play an important role in the occurrence of GCA through Wnt / β-catenin signaling pathway.