The Correlation Between Malignant Glioma MGMT Protein Expression And Serum Methylated MGMT Gene Promoter And Their Impact To Temozolomide (TMZ) Chemotherapy

Objective:Malignant gliomas is the most common primary tumors,high mortality rate.Alkylating agent chemotherapy of malignant glioma is one of commonly used drugs,but because of higher tumor drug resistance,the clinical efficacy is unsatisfactory.Recent studies have shown that alkylating agent resistance mainly due to DNA repair protein 6-O-methyl-guanine-DNA methyltransferase(MGMT) exists.Since MGMT can repair specific tumor cell damage induced by alkylating agent,leading to drug resistance.However,the correlation between serum MGMT gene promoter methylation and MGMT protein in tumor tissue and the impact of chemotherapy has unclarified.This study on the the correlation between serum MGMT gene promoter methylation and tumor tissue in the expression of MGMT protein and their impact to temozolomide(TMZ) chemotherapy were studied.Materials and methods:The study for the tumor hospital of yunnan procince in June 2008 to June 2009 38 patients'(diagnosed as malignant glioma WHO gradeⅢ,Ⅳ)tumor tissue and serum,tumor tissue for MGMT Immunohistochemistry,determination of tumor MGMT expression and salt extraction of 38 patients were analyzed preoperative serum DNA,then the serum was determined MSP MGMT gene promoter methylation status.Also selected 10 HICH patients' brain tissue and serum samples as a control group.Therefore,selected patients with malignant glioma is surgery, radiotherapy,and chemotherapy by temozolomide(TMZ).Assessment of efficacy evaluation,were divided into two types according to clinical situations:(1)effective(CR+PR):refers to the treatment effect after 6 months of good or stable disease:(2) invalid(MR+SD+PD):refers to the treatment later,the patient improved temporarily,but the short-term(6 months) recurrence,using SPSS12.0 data statistical analysis software for statistical analysis between the two groups usingχ~2 test or Fisher's exact probability test,correlation test,using Spearman correlation coefficients,analysis of P＜0.05 for the difference was significant.Results:(1) 22 patients in 38 patients MGMT express positive,the expression rate was 57.9%,the effective rate was 16.7%,invalid group the expression rate was 95%.The expression of MGMT in different patients chemotherapy effect was significant(P＜0.05),the diffreet expression of MGMT had diffreent curative effect.(2) 17 patients' serum MGMT gene promoter methylation masculine expression in 38 cases,expression rate was 44.7%,effective group serum MGMT gene promoter methylation positie rate was 88.9%,but in invalid group the rate was 5%.The diffreent Serum MGMT gene promoter methylation expression in patients the curative effect was statistically significant(P＜0.05),serum MGMT gene promoter methylation expression had influence to curative effect by TMZ(3) male patients' tumor tissue MGMT expression rate was 60%,female patients' was 55.6%,Male patients' serum MGMT gene promoter methylation expression rate was 45.0%,female patients' was 44.4%;＜40 age patients' tumor tissue expression MGMT rate was 60%,≥40 age patients' rate was 53.8%;＜40 age patients' serum MGMT gene promoter methylation rate was 46.2%,≥40 age patients' rate was 44%;Ⅲgliomas' tumor tissue MGMT expression rate was 56.5%,Ⅳgliomas' rate was 60%,Ⅲgliomas' serum MGMT gene promoter methylation expression rate was 43.5%,Ⅳgliomas' rate was 46.7%;usingχ~2 inspection to the statistical analysis,(P＞0.05).Serum MGMT gene promoter methylation and tumor tissue MGMT expression was unrelated with gender,age and pathological type.(4) 22 cases MGMT tumor tissue in patients with positive serum MGMT gene promoter methylation is only 2 cases,methylation rate was 9.1%,in 16 cases of patients with negatie MGMT expression 15 patients serum MGMT gene promoter methylation, methylation rate was 93.8%.Use Spearman correlation coefficient analysis,(P＜0.05),serum MGMT gene promoter methylation and tumor tissue MGMT expression to have correlation.(5)10 cases of cerebral patients in the brain HICH MGMT express negative or positive suspicious which were significant differences from malignant glioma tissue MGMT expression,and there were fails to detect MGMT in serum.Conclusion:1.serum MGMT gene promoter methylation and MGMT expression in tumor tissues was a negative correlation between serum MGMT gene promoter methylation of tumor tissue MGMT.2.serum MGMT gene promoter methylation and tumor tissue MGMT positive expression-negative patients with good effect on TMZ,the contrary effect of the poor.3.serum MGMT gene promoter methylation and tumor MGMT expression and gender,pathological type,no correlation.4.no pathological diagnosis made by surgical patients,serum levels of MGMT gene promoter methylation can be guided to the choice of individual chemotherapy.