肺腺癌中DNMT1表达和TFF1甲基化水平的相关性及临床意义  

Expression Level of DNMT1 in Lung Adenocarcinoma and Its Correlation with TFF1 Gene Methylation Level and Clinical Significances

作　　者：郭超 法楠 黄景涛 侯继申[3] 梁宗英[3] 孙光蕊[3] GUO Chao(Baoding No.2 Central Hospital,Hebei Baoding 072750,China)

机构地区：[1]河北省保定市第二中心医院,河北保定072750 [2]河北省丰宁满族自治县医院,河北丰宁068350 [3]承德医学院附属医院,河北承德067000

出　　处：《河北医学》2025年第3期420-425,共6页Hebei Medicine

基　　金：河北省医学科学研究课题计划,(编号:20231361)。

摘　　要：目的:探讨肺腺癌组织中DNA甲基转移酶1(DNMT1)表达与三叶因子1(TFF1)甲基化水平及临床意义。方法:选取人肺腺癌组织,采用焦磷酸测序法检测TFF1甲基化水平,实时荧光定量聚合酶链反应(RT-qPCR)检测TFF1和DNMT1 mRNA相对表达量,采用免疫组化及Western blot检测TFFI和DNMT1的蛋白表达。统计学方法分析TFF1甲基化水平和DNMT1表达与临床病例特征的关系。结果:与癌旁组织相比,癌组织中TFF1基因甲基化率显著升高(P<0.05)。PCR结果显示,与癌旁组织相比,癌组织中TFF1 mRNA相对表达量下降,DNMT1 mRNA相对表达量显著升高(P<0.05)。免疫组化结果显示,与癌旁组织相比,TFF1蛋白在癌组织中呈低表达,而DNMT1蛋白呈高表达(P<0.05)。Western blot结果显示,与癌旁组织相比,癌组织中TFF1蛋白表达率降低,DNMT1蛋白表达率上升(P<0.05)。TFF1甲基化和DNMT1表达与肿瘤TNM分期和淋巴结转移关系密切(P<0.05)。统计分析结果显示,肺腺癌组织中TFF1甲基化和DNMT1蛋白表达具有相关性,二者呈正相关(r=0.538,P<0.05)。结论:在肺腺癌病变过程中DNMT1与TFF1基因甲基化关系密切,DNMT1高表达和TFF1高甲基化共同作用可能促进了肺腺癌的发生和发展。Objective:To measure the expression level of DNA methyltransferase 1(DNMT1)and the methylation level of trefoil factor 1(TFF1)in lung adenocarcinoma,and to analyze their clinical significances.Methods:The methylation level of TFF1 in human lung adenocarcinoma tissues was detected by pyrosequencing.The mRNA levels of TFF1 and DNMT1 were detected by reverse transcription coupled to the quantitative polymerase chain reaction(RT-qPCR).Their protein levels were detected by immunohistochemical staining and Western blot.The correlation of the methylation level of TFF1 and expression level of DNMT1 with pathological characteristics of lung adenocarcinoma was explored.Results:The methylation rate of the TFF1 gene was significantly higher in the lung adenocarcinoma tissues compared with that of paracancerous tissues(P<0.05).PCR results showed that the mRNA level of TFF1 was significantly lower in the lung adenocarcinoma tissues,while that of DNMT1 was significantly higher than those of paracancerous tissues(P<0.05).Immunohistochemistry showed a significantly lower protein level of TFF1,but higher protein level of DNMT1 in the lung adenocarcinoma tissues than those of paracancerous tissues(P<0.05).Western blot results showed a significantly lower protein level of TFF1,but higher protein level of DNMT1 in the lung adenocarcinoma tissues than those of paracancerous tissues(P<0.05).TFF1 methylation level and DNMT1 expression were significantly correlated with the TNM staging and lymph node metastasis of lung adenocarcinoma(P<0.05).The statistical analysis showed that TFF1 methylation and DNMT1 protein expression were related in lung adenocarcinoma tissues,it was positive correlation(r=0.538,P<0.05).Conclusion:During the cancerous progression of lung adenocarcinoma,DNMT1 is closely linked with methylation of the TFF1 gene.High level of DNMT1 and high methylation level of TFF1 both promote the occurrence and development of lung adenocarcinoma.

关 键 词：肺腺癌 DNMT1 TFF1 甲基化修饰 表观遗传学 

分 类 号：R73[医药卫生—肿瘤]