Promoter Methylation Of GSTP1 And MDR1 Gene In Lung Adenocarcinoma And Its Correlation With DNMT1 Expression And Their Prognosis Significance

【Objective】To detect promoter methylation of GSTP1 and MDR1 genes and protein expression of GST-π,Pgp and DNMT1 in lung adenocarcinoma.To investigate the role of promoter methylation of GSTP1,MDR1 genes during lung adenocarcinoma carcinogenesis,the relationship between promoter methylation of GSTP1,MDR1 genes and GST-π,Pgp and DNMT1 protein expression,and the value of promoter methylation of GSTP1,MDR1 genes and DNMT1 protein expression for patient's prognosis.【Methods】The CpG island methylation status of GSTP1,MDR1 genes were analyzed in 95 cases of tumor specimens and 10 cases normal tissues using methylation-specific polymerase chain reaction(MSP).DNMT1,GSTP1,MDR1 protein expression were determined by immunohistochemistry in 95 cases of lung tumor specimens,their adjacent tissues and 10 normal lung tissues.The patients were followed up,and the overall-survival rate and 3-year survival rate were calculated.All the Statistical analysis data were analyzed by SPSS13.0.【Results】The promoter methylation of GSTP1 gene were detected in 29 of 95 (30.5%) lung adenocarcinoma cases,and MDR1 gene were detected in 64 of 95 cases(67.4%).In the same time,unmethylation of GSTP1 gene and methylaiton of MDR1 gene were all detected in 10 nomal tissues cases.And there were significant difference between nomal lung tissues and lung adenocarcinoma(P＜0.05).48 cases showed DNMT1-positive,39 cases showed MDR1-positive,and 60 cases showed GSTP1-positive in 95 cases of lung adenocarcinoma with positive rates of 50.5%, 41.1%,63.1%respectively.There're significant negative correlation between the methylation statue of GSTP1,MDR1 genes and their protein expression(P＜0.05). This indicates that gene promoter hypermethylaiton of GSTP1,MDR1 reduces the protein expression,and gene hypomethylation increase the protein expression.No correlation was found between the methylation statue of GSTP1,MDR1 genes and patient age,gender,smoking,lymph node metabasis,tumor type,clinic stage (P＞0.05).There's significant negative correlation between protein expression of DNMT1 and promoter methylation of GSTP1 gene(P＜0.05),and no relativity with promoter methylation of MDR1 gene(P＞0.05).Overall-survival rate and 3-year survival rate were 43.90%,51.22%respectively in patients with DNMT1 positive expression by Kaplan-Meier,compared with 66.26%,74.54%in patients with DNMT1 negative expression.DNMT1 positive expression could serve as an unfavourable indicater for patients with lung adenocarcinoma by Log-Rank(P＜0.05).Overall-survival rate and 3-year survival rate were 64.01%, 69.83%in patients with MDR1 methylation,and 24.87%,49.74%cases showed MDR1 unmethylation,with statistically significance difference between them(P＜0.05).The Cox's proportional hazard regression model revealed that overexpression of DNMT1 protein,hypomethylation of MDR1 promoter were independently associated with unfavourable prognosis.【Conclusion】1.Promoter of MDR1 gene was detected hypomethylation in lung adenocarcinoma,while promoter of GSTP1 gene showe hypermethylation.2.Gene promoter hypermethylation of GSTP1,MDR1 reduces the protein expression,and gene hypomethylaiton increases the protein expression.3.The methylation of GSTP1 and MDR1 were not induced by DNMT1,and might be induced by other pathways.4.Overexpression of DNMT1 and hypomethylation of MDR1 promoter might serve as an unfavourable indicater for patients with lung adenocarcinoma.