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目的体轴抑制因子(Axin)是Wnt信号传导通路的关键抑制因子,其基因启动子区存在CpG岛,本研究的目的是探讨非小细胞肺癌组织中Axin基因启动子区是否存在异常高甲基化,以及高甲基化对Axin转录水平的影响,及其与肺癌患者临床病理因素的关系。方法应用巢式甲基化特异性PCR(Nested MSP)对98例肺癌组织及其配对癌旁正常肺组织中Axin基因启动子区的甲基化状态进行了检测,同时应用RT-PCR方法检测了肺癌组织及其配对癌旁正常肺组织中Axin mRNA的水平,并且通过卡方检验统计Axin基因启动子区高甲基化状态与肺癌患者临床病理因素的关系。结果部分非小细胞肺癌组织中Axin基因启动子区处于高甲基化状态(42/98),而其配对的癌旁正常肺组织中Axin基因处于半甲基化或非甲基化状态(56/98),高甲基化的肺癌组织中Axin mRNA的水平明显低于其配对癌旁正常肺组织及非高甲基化的肺癌组织中Axin mRNA的水平;Axin基因启动子区异常高甲基化与非小细胞肺癌患者的分化程度负向关,与TNM分期及淋巴结转移正相关。结论非小细胞肺癌中Axin基因启动子区高甲基化与Axin的转录水平和非小细胞肺癌的分化程度负相关,与TNM分期及淋巴结转移正相关。
Axin is a key inhibitor of Wnt signaling pathway, and its gene promoter region exists CpG island. The purpose of this study is to investigate whether there is abnormal hypermethylation of Axin gene promoter region in non-small cell lung cancer, As well as the influence of hypermethylation on Axin transcription and its relationship with clinicopathological factors in patients with lung cancer. Methods The methylation status of Axin gene promoter region in 98 cases of lung cancer tissues and matched normal lung tissues was detected by nested methylation-specific PCR (Nested MSP), and RT-PCR was used to detect the methylation status Axin mRNA levels in lung cancer tissues and paired para-cancerous normal lung tissues, and the relationship between the hypermethylation status of Axin gene promoter region and the clinicopathological factors of lung cancer patients were analyzed by Chi-square test. Results Axin gene promoter region was hypermethylated (42/98) in some non-small cell lung cancer tissues, while Axin gene in paired non-small cell lung cancer tissues was in semi-methylated or unmethylated state (56/98 ). Axin mRNA levels in hypermethylated lung cancer tissues were significantly lower than those in paired normal lung tissues and non-hypermethylated lung cancer tissues. Axin gene promoter hypermethylation was significantly associated with non-small cell lung cancer The degree of differentiation negatively correlated with TNM staging and lymph node metastasis. Conclusion The hypermethylation of Axin gene promoter region in non-small cell lung cancer is negatively correlated with Axin transcription and differentiation of non-small cell lung cancer, and positively correlated with TNM stage and lymph node metastasis.