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目的:探讨人贲门腺癌(gastric cardia adenocarcinoma,GCA)组织中胰岛素样生长因子结合蛋白-7(insulin-likegrowth factor binding protein 7,IGFBP7)基因启动子区及第1外显子区甲基化状态及其与IGFBP7蛋白表达之间的关系。方法:选取河北医科大学第四医院2009年4月至2011年12月间收治的85例GCA患者癌组织标本和67例癌旁组织标本。采用甲基化特异性聚合酶链式反应(methylation specific polymerase chain reaction,MSP)方法、RT-PCR及免疫组织化学法检测IGFBP7基因在GCA组织及癌旁组织中的甲基化情况、IGFBP7 mRNA及蛋白的表达。结果:GCA组织中IGFBP7基因启动子区甲基化率为52.9%(45/85),第1外显子5’非翻译区的甲基化率为35.3%(30/85),相应癌旁组织IGFBP7基因启动子区及第1外显子5’非翻译区的甲基化率分别为35.8%(24/67)和19.4%(13/67);癌组织IGFBP7基因启动子区及第1外显子5’非翻译区的甲基化率明显高于癌旁组织(P<0.05),且GCA组织中IGFBP7基因启动子区甲基化率显著高于第1外显子区(P<0.05)。GCA组织中IGFBP7 mRNA和蛋白表达显著低于癌旁组织(P<0.05),且与其启动子区甲基化状态呈负相关。结论:GCA组织中IGFBP7基因启动子区比第1外显子区更易发生甲基化而导致IGFBP7表达缺失,IGFBP7基因启动子区异常高甲基化可能是GCA发生的机制之一。
Objective: To investigate the methylation status of promoter region and exon 1 region of insulin-like growth factor binding protein-7 (IGFBP7) gene in gastric cardia adenocarcinoma (GCA) And its relationship with IGFBP7 protein expression. Methods: Eighty-five GCA specimens from 67 patients with GCA were collected from April 2009 to December 2011 in the Fourth Hospital of Hebei Medical University. Methylation-specific polymerase chain reaction (MSP) was used to detect the methylation status of IGFBP7 gene in GCA tissues and paracancerous tissues by RT-PCR and immunohistochemistry. IGFBP7 mRNA and Protein expression. Results: The methylation rate of IGFBP7 gene promoter region was 52.9% (45/85) in GCA tissues, and 35.3% (30/85) in the 5 ’untranslated region of exon 1, corresponding to adjacent cancer The methylation rates of IGFBP7 gene promoter region and exon 1 5 ’untranslated region were 35.8% (24/67) and 19.4% (13/67), respectively. The promoter region of IGFBP7 gene and the The methylation rate of 5 ’untranslated region in exon was significantly higher than that in paracancer (P <0.05), and the methylation rate of IGFBP7 promoter in GCA was significantly higher than that in exon 1 (P < 0.05). The expression of IGFBP7 mRNA and protein in GCA tissues was significantly lower than that in paracancerous tissues (P <0.05), and negatively correlated with the methylation status of its promoter region. CONCLUSION: The promoter region of IGFBP7 gene in GCA tissue is more likely to methylate than exon 1 region, leading to the loss of IGFBP7 expression. Abnormal hypermethylation of IGFBP7 gene promoter region may be one of the mechanisms of GCA.