结肠癌组织FOXF1基因甲基化检测及其临床意义  

Detection of FOXF1 gene methylation in colon cancer and its clinical significance

作　　者：温机智[1] 韩晓燕[1] 卫洪波[2] 陆慧琼[1] 张富程[1] 

机构地区：[1]中山大学附属第三医院中心实验室,广州510630 [2]中山大学附属第三医院胃肠外科,广州510630

出　　处：《新医学》2013年第6期370-373,共4页Journal of New Medicine

基　　金：广东省科技计划项目(2009B030801091);广州市科技计划项目(2011J4100105)

摘　　要：目的研究结肠癌组织中叉头框F1基因(FOXF1)启动子区甲基化状态及其临床意义,探讨其在结肠癌发生发展中的作用。方法应用甲基化特异性PCR检测62例结肠癌标本中FOXF1基因启动子区甲基化状态,并分析其与结肠癌患者临床病理特征的关系。采用实时荧光定量PCR检测结肠癌标本中FOXF1基因mRNA表达水平,并分析FOXF1基因甲基化与其mRNA表达间的关系。结果结肠癌组织中FOXF1基因启动子区甲基化率为64.5%(40/62),显著高于正常黏膜组织的4.8%(3/62),差异具有统计学意义(P<0.01),低分化组中FOXF1甲基化率为82.6%(19/23),高于高中分化组的53.8%(21/39),差异具有统计学意义(P<0.05)。结肠癌组织中FOXF1基因mRNA相对表达量为1.453±0.385,显著低于正常黏膜组织的3.648±1.228,差异具有统计学意义(P<0.01)。结肠癌组织中FOXF1基因甲基化状态与FOXF1基因mRNA表达呈负相关(rs=-0.438,P<0.01)。结论 FOXF1基因启动子异常甲基化及其mRNA表达下调是结肠癌中的频发分子事件;也是导致FOXF1基因mRNA表达下调的机制之一;FOXF1基因在不同分化程度的结肠癌患者中甲基化率不同,提示FOXF1基因甲基化状态有可能成为评价结肠癌恶性程度的辅助指标,FOXF1基因也可能成为结肠癌靶向治疗的潜在靶点。Objective To investigate the DNA promoter methylation status of Forkhead box F1 （ FOXF1 ） in colon cancer and its clinical significance. Methods Methylation status of FOXFl promoter re-gion was detected by methylation-specific polymerase chain reaction （MSP） in colon cancer surgical specimens （ n = 62） , and its correlations with clinicopathological parameters of colon cancer patients were also analyzed. The expression level of FOXFl mRNA in colon cancer specimens was detected by real-time fluorescent quanti-tative polymerase chain reaction; the association of methylation status of FOXFl promoter with FOXFl mRNA expression was also investigated. Results Methylation frequency of FOXF1 promoter was significantly higher in colon cancer tissues （64. 5% ） than in normal colon mueosa tissues （4. 8% , P 〈 0. 01 ）. Methylation of FOXF1 was observed more frequently in patients with advanced histological grades than in patients with less ad-vanced histological grades （P 〈 0. 05 ）. The relative expression level of FOXFl mRNA was significantly de-creased in colon cancer tissues （ 1. 453 ± 0. 385 ） compared with adjacent normal colon mucosa tissues （3. 648 ± 1. 228, P 〈0. 01 ）. Methylation status of FOXFl1 promoter was inversely associated with FOXFI mRNA ex-pression （rs = 0. 438, P 〈 0. 01 ）. Conclusions Aberrant methylation of FOXF1 promoter is a molecular e-vent that frequently occurred in the carcinogenesis of colon cancer, which may be an important factor in down-regulation of FOXFl mRNA expression. Methylation of FOXFl is observed more frequently in patients with ad-vanced histological grades, suggesting that it may be an adjunctive marker for colon cancer. FOXFl can also be a potential therapeutic target for colon cancer.

关 键 词：结肠肿瘤 甲基化 实时荧光定量聚合酶链反应 叉头框F1基因 

分 类 号：R735.35[医药卫生—肿瘤]