Relationship Between Promoter Methylation Of DAPK Gene And DNMT1 Expression In Gastric Cancer

ObjectiveTo investigate the relationship between the expression of DNA methyltransferase1(Dnmt1)and Death associated protein kinase(DAPK)gene methylation in gastric cancer.Method80 patients with gastric cancer were enrolled in our study.All samples'cancerous and corresponding adjacent normal gastric mucosa were obtained surgically and confirmed pathologically.Using methylation-specific PCR(MSP)to detect the methylation status of DAPK gene promoter and using RT-PCR to detect mRNAs expression of DAPK and DNMT1 gene.The expression of DAPK and DNMT1 proteins were analysed by immunohistochemistry.ResultsAmong the 80 patients,48 cases showed a methylation of DAPK promoter in samples of tumorous tissue,the methylation positive rate is 60%,while 10 cases showed a methylation of DAPK promoter in samples of the corresponding adjacent normal tissue,the methylation frequency is 12.5%,there were significant difference in methylation rate between tumor tissues and their corresponding adjacent normal tissues(?~2=39.053,p<0.01).There was no significant difference between age?gender?tumor size and the DAPK methylation status in tumorous tissue(p>0.05),but TNM stage?differentiation degree and lymph node metastasis were correlated with it.In gastric cancer,the positive rate of Dnmt1mRNA expression was 85%(68/80),it was significant higher than in corresponding adjacent normal tissue(5/80,6.25%),while the positive rates of DAPK mRNA expression in gastric cancer(20/80,25%)were significantly lower than that in corresponding adjacent normal tissue(75/80,93.75%).DAPK protein showed a significantly lower level in tumorous tissue than in corresponding adjacent normal tissue(12.5%vs 97.5%),while Dnmt1 protein showed a significantly higher level(87.5%vs 10%)in tumorous tissue than in corresponding adjacent normal tissue.The expression of DAPK protein has a negative correlation with that of Dnmt1 protein(r=-0.391,p<0.01).ConclusionThe overexpression of DNMT1 gene may result in the promoter hypermethylation of the DAPK gene,thus reduced the expression of its mRNA and protein,which may be associated with the occurrence of gastric cancer.