非小细胞肺癌中Axin基因启动子区异常高甲基化与临床病理因素的关系  

Abnormal hypermethylation of Axin gene promoter region in non-small cell lung cancer correlates with clinicopathological characteristics

作　　者：杨连赫[1] 张婉琳[1] 沈帅[1] 于承仟 王雪[1] 

机构地区：[1]中国医科大学附属第一医院病理科,基础医学院病理学教研室,辽宁沈阳110001

出　　处：《解剖科学进展》2016年第6期587-590,共4页Progress of Anatomical Sciences

基　　金：国家自然科学基金(81301930);辽宁省教育厅科学研究一般项目(L2015595)

摘　　要：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。Objective Axis inhibitory factor（Axin） is a key inhibitor of Wnt signaling pathway, CpG island is found in its promoter region. The purpose of this study is to investigate the methylation status of non-small cell lung cancer, and the relationship between Axin gene hypermethylation and its transcriptional level, as well as the relationship between hypermethylated Axin gene and clinicopathological characteristics. Methods We applied nested methylation-specific PCR（Nested MSP） in 98 cases of lung cancer tissues and their matched adjacent normal lung tissue to detect Axin promoter region methylation status, Axin mRNA levels in these tissues were detected by RT-PCR. The relationship between Axin hypermethylation status and clinicopathological factors in lung cancer patients was tested by chi-square test. Results Hypermethylated Axin gene promoter was found in non-small cell lung cancer（42/98）, Axin gene promoter was in semi-state or unmethylated state in its paired adjacent normal lung tissues（56/98）, Axin mRNA level in hypermethylated lung cancer tissues were significantly lower than that in their paired adjacent normal lung tissues and non-hypermethylated lung cancer tissues. Axin gene promoter hypermethylation negatively correlated with the diferentiafion level of lung cancer, but positively correlated with TNM stage and lymph node metastasis. Conclusion Hypermethylated Axin gene promoter negatively correlated with Axin transcriptional level and the degree of differentiation, positively correlated with TNM stage and lymph node metastasis.

关 键 词：甲基化 非小细胞肺癌 体轴抑制因子 

分 类 号：R734.2[医药卫生—肿瘤]