乳腺癌Runx3基因启动子甲基化状态及其与病理特征的关系

目的探讨乳腺癌组织中Runx3基因启动子甲基化状态及其与乳腺癌临床病理特征之间的关系。方法 2007年2月至2009年4月收集经病理确诊的56例乳腺癌患者癌组织及相应的癌旁组织。采用甲基化特异聚合酶链反应检测Runx3基因启动子区CpG岛的甲基化状态,并检测其对Runx3基因表达的影响和分析其与乳腺癌临床病理特征之间的关系。统计学分析采用χ2检验和Pearson相关分析法。结果乳腺癌组织中Runx3基因启动子区CpG岛甲基化率(55.4%)显著高于癌旁组织中的甲基化率(10.7%),二者之间差异有统计学意义(χ2=25.225,P=0.000)。Runx3基因的异常甲基化和乳腺癌患者的临床分期及淋巴结转移有关(P=0.018,P=0.010),但与患者的年龄、肿瘤直径大小及组织学类型无关(P0.050)。Runx3mRNA表达与Runx3启动子甲基化呈弱相关(r=0.343,P=0.010)。结论 Runx3基因启动子甲基化状态导致Runx3基因mRNA表达降低或缺失。Runx3基因启动子区甲基化可能是导致Runx3基因在乳腺癌中失活的分子机制之一。

Analysis of the status of Runx3 gene promoter methylation in breast cancer and its relationship with pathological features

Objective To analyze the status of Runx3 gene promoter methylation and explore its association with the expression of Runx3 gene and clinicopathological factors of breast cancer. Methods From February 2007 to April 2009, a total of 56 breast cancer tissue samples and corresponding pericancer tissues were collected and used for this study. All samples were confirmed pathologically. Methylation-speeific PCR （polymerase chain reaction） was performed to detect the promoter hypermethylation of Runx3 gene, and analyze its influence on the expression of Runx3 gene and the relationship between Runx3 promoter methylation and clinicopathological factors in breast cancer. Chi-square test and Pearson test were used for statistical analysis. Results The rate of promoter hypermethylation of Runx3 gene in the breast cancer tissues （55. 4%） was significantly higher than that in the pericancer tissues （10. 7%）, with statistical difference between the two （x2= 25.225, P = 0. 000）. Runx3 gene hypermethyIation was related with clinical staging and lymph node metastasis （P=0. 018,P=0. 010）, but not related with the age, turnout size and histological types （P〉0. 050）. There was a light association between the expression of Runx3 mRNA and Runx3 promoter methylation （r=0. 343, P= 0. 010）. Conclusions Runx3 promoter methylation can lead to a decrease or absence in the runx3 mRNA expression in breast cancer. The promoter methylation of Runx3 gene can induce the inhibition of Runx3 mRNA expression, which might he one of the mechanisms of Runx3 gene inactivation in human breast cancer.