基质金属蛋白酶-9基因启动子甲基化在非小细胞肺癌治疗中的作用  

Role of matrix metalloproteinases-9 promoter DNA methylation in the treatment of non-small cell lung cancer

作　　者：桑圣刚[1] 胡敏[2] 荣红[2] 

机构地区：[1]海南医学院热带医学与检验医学院,海南海口570102 [2]海南医学院附属医院,海南海口570102

出　　处：《中华肺部疾病杂志（电子版）》2013年第3期35-38,共4页Chinese Journal of Lung Diseases(Electronic Edition)

基　　金：海南省重点项目(ZDXM20100046);海南省卫生厅项目(琼卫2008-61)

摘　　要：目的探讨基质金属蛋白酶-9(MMP-9)基因启动子甲基化在非小细胞肺癌(NSCLC)治疗中的作用。方法采用甲基化特异性聚合酶链反应(PCR)检测NSCLC患者及健康人外周血白细胞MMP-9启动子的甲基化状态。用酶联免疫吸附(ELISA)法测定血浆MMP-9的含量及RT-PCR检测外周血白细胞中MMP-9mRNA的表达水平。结果 NSCLC组MMP-9基因启动子平均甲基化密度显著降低,与对照组相比有显著性差异(23.5±4.7vs40.6±3.8,P<0.05);NSCLC组MMP-9mRNA表达显著增强,与对照组相比有显著性差异(1.35±0.31vs0.76±0.07,P<0.05);NSCLC组MMP-9含量显著增高,与对照组相比有显著性差异(597±143vs242±65,P<0.05)。MMP-9甲基化状态与NSCLC患者的肿瘤组织类型、TNM分期无关(P>0.05);MMP-9mRNA表达及MMP-9蛋白水平与NSCLC的组织类型无关(P>0.05),但和TNM的分期有关:Ⅲ期、Ⅳ期MMP-9mRNA表达及MMP-9蛋白水平均明显高于Ⅱ期(P>0.05)。经相关性分析,MMP-9mRNA表达与其基因启动子甲基化密度变化成正相关(R=0.79,P<0.05);MMP-9含量与其基因启动子甲基化密度变化成正相关(R=0.82,P<0.05);MMP-9含量与MMP-9mRNA的表达成正相关(R=0.77,P<0.05)。结论 NSCLC患者MMP-9基因启动子处于低甲基化状态,其通过增强MMP-9mRNA表达及促进MMP-9蛋白分泌在肿瘤的发生发展中发挥作用。Objective To explore the role of matrix metalloproteinases-9 （MMP-9） promoter DNA methylation in the treatment of non-small cell lung cancer （NSCLC）. Methods MMP-9 promoter DNA methylation was detected in NSCLC patients and control group by methylation-specific polymerase chain reaction （PCR）. Plasma MMP-9 levels were quantified with enzyme-linked immuno sorbent assay（ELISA） ; and mRNA expression of MMP-9 extracted from mononuclear cell were detected by RT-PCR method. Results AS compared with control group, there was the lower level of the average density of the DNA methylation of the MMP-9 gene promoter in the NSCLC patients （23.5 ± 4.7 vs 40.6 ± 3.8, P 〈 0.05）. the plasma concentration of MMP-9 were higher in the NSCLC patients （597 ± 143 vs 242 ± 65, P 〈 0.05 ）. The MMP-9 mRNA expressions were obviously amplified（1.35 ± 0. 31 vs 0. 76 ± 0.07, P 〈 0. 05）. The promoter methylation status of MMP-9 was not significantly correlated with histological type and TNM stage（P 〉0.05）, The MMP-9 mRNA expressions and the concentration of MMP-9 were not significantly correlated with histological type, but they were correlated with TNM stage ： they were significantly higher in Ⅲ, Ⅳ than Ⅱ （P 〈 0. 05 ）. By linear correlation analysis ： The MMP-9 mRNA expressions was positive correlation with the average density of the DNA methylation of the MMP-9 （R = 0.79, P 〈 0.05 ）. the concentration of MMP-9 was positive correlation with the average density of the DNA methylation of the MMP-9 （R = 0.82, P 〈 0.05）. The concentration of MMP-9 was positive correlation with the MMP-9 mRNA expressions （R = 0.77, P 〈 0.05）. Conclusions MSP analysis shows the promoter methylation of MMP-9 is low status. The results suggest that MMP-9 promoter methylation plays a key role in NSCLC development through enhance the expression and protein level of MMP-9.

关 键 词：非小细胞肺癌 基质金属蛋白酶-9 甲基化 

分 类 号：R734.2[医药卫生—肿瘤]