乳腺癌组织中AXIN2基因启动子区甲基化表达及临床意义

目的本研究旨在通过检测乳腺癌组织中AXIN2基因启动子区甲基化状态,分析其与乳腺癌相关危险因素、临床病理特征及mRNA表达间的关系,探讨其在临床应用中的价值。方法选取2018年1月至2019年12月在山东第一医科大学附属肥城市人民医院普外科经手术切除治疗的84例女性乳腺癌患者的乳腺癌组织和癌旁组织,检测组织的AXIN2基因启动子的甲基化状态和mRNA表达量,使用不同浓度的甲基转移酶抑制剂(5-Azacytidine,5-Aza)处理人乳腺癌ZR-75-1细胞,且进行乳腺癌相关危险因素和临床病理特征的收集与分析。结果乳腺癌组织的AXIN2基因启动子甲基化阳性率(40.5%)显著高于癌旁组织的甲基化阳性率(19.0%)(χ2=10.401,P=0.001)。AXIN2甲基化阳性率与乳腺癌患者的初产年龄(χ2=5.467,P=0.019)、是否有人工流产史(χ2=8.372,P=0.006)有关;AXIN2甲基化阳性率与是否发生淋巴结转移(χ2=5.338,P=0.021)、ER表达状态(χ2=9.141,P=0.002)及PR表达状态(χ2=6.918,P=0.009)有关。此外,乳腺癌组织的AXIN2基因mRNA相对表达量(00.22±0.03)显著低于癌旁组织的mRNA相对表达量(0.46±0.06)(t=3.527,P<0.001);甲基化阳性乳腺癌组织的mRNA相对表达量(0.13±0.02)显著低于甲基化阴性乳腺癌组织的mRNA相对表达量(0.29±0.04)(t=3.616,P<0.001)。ZR-75-1细胞使用5-Aza处理后,AXIN2基因mRNA相对表达量显著升高(t=3.824,P<0.001)。结论AXIN2基因启动子区DNA甲基化与乳腺癌发生机制有关,在临床中有一定应用价值。

Expression and significance of AXIN2 gene promoter methylation in breast cancer

Objective To analyze the relationship between the AXIN2 gene promoter methylation status in breast cancer tissues with the breast cancer-related risk factors,clinicopathological characteristics and the mRNA expression of AXIN2 gene.Methods The breast cancer tissues and adjacent tissues of 84 breast cancer patients were taken to detect the AXIN2 gene promoter methylation status and the AXIN2 mRNA expression.We used different concentrations of methyltransferase inhibitors 5-Azacytidine(5-Aza)to treat human breast cancer ZR-75-1 cells,and collected the breast cancer-related risk factors and clinicopathological characteristics.Results The positive rate of methylation of AXIN2 gene promoter in breast cancer tissues(40.5%)was significantly higher than that of adjacent tissues(19.0%)(χ2=10.401,P=0.001).The positive rate of AXIN2 methylation was related to the age at first delivery(χ2=5.467,P=0.019)and a history of induced abortion(χ2=8.372,P=0.006);the positive rate of AXIN2 methylation was related to lymph node metastasis(χ2=5.338,P=0.021),ER expression status(χ2=9.141,P=0.002)and PR expression status(χ2=6.918,P=0.009).In addition,the relative expression of AXIN2 gene mRNA in breast cancer tissues(0.22±0.03)was significantly lower than that in adjacent tissues(0.46±0.06)(t=3.527,P<0.001).The relative mRNA expression of the methylation-positive breast cancer tissues(0.13±0.02)was significantly lower than that of the methylation-negative breast cancer tissues(0.29±0.04)(t=3.616,P<0.001).After ZR-75-1 cells treated with 5-Aza,the relative expression of AXIN2 gene mRNA increased significantly(t=3.824,P<0.001).Conclusion DNA methylation in the promoter region of the AXIN2 gene is related to the pathogenesis of breast cancer,and has certain clinical application value.