Glioma MGMT Promoter Methylation, MGMT Protein And NF-κb Expression And Their Significance

Background and objective: Cerebral glioma is one of the commonest primary intracranial tumors, and the proportion is about50%-60%. The cerebral glioma grows diffusively, without obvious limit among the surrounding brain tissue, so it has unfavorable prognosis and short life cycle. Improving the life time of the patient has always been the important and difficult issue of studies. Recent researches have showed that the growth and differentiation of glioma are connected with abnormal expressions of some tumor-related genes. The therapies are mainly surgical resection, radiotherapy, and chemotherapy. Chemotherapy plays a key role among comprehensive therapies, but the drug resistance affects its efficiency. Some studies suggest that O6-methylguanine-DNA methyltransferase (MGMT) activity alters along with the chemoresistance of tumor to alkylating agents. Nuclear factor Kappa B (NF-κb), the dominant nuclear transcription factor which helps many factors to transcript and express, closely affects the tumor’s growth, reproducing and apoptosis. Some researches point out that in cerebral glioma, NF-κb might induce the generation of MGMT, so as to reinforce the chemoresistance of tumor to alkylating agents. In this study, immunohistochemistry assay is conducted to detect the expression of MGMT and NF-κb in gliomas; methylation specific PCR (MSP) is used to analyze the MGMT promoter methylation in cerebral glioma. In this way, the paper aims to explore the correlation of MGMT promoter methylation and MGMT protein expression, the relevance of MGMT and NF-κb expression, and the relation of cerebral glioma clinical results and pathological grades.Materials and Methods:Taking42pathological paraffin samples to assay the expression of MGMT and NF-Kb in different gliomas and using MSP analysis to study MGMT promoter methylation in these42samples. In this way, the paper aims to explore the correlations between both the MGMT and NF-Kb proteins and the gliomas grades and to test the correlation between MGMT and NF-Kb, and the relation between MGMT promoter methylation and MGMT protein.Results:1. The rate of MGMT expression is45.2%and MGMT expression is different in diverse grades of gliomas(p<0.05), for example, as the malignancy of glioma increases, MGMT expression decreases.2. The total rate of NF-Kb expression is59.5%, but NF-Kb expression has no relation with the grades of glioma (p>0.05).3. In the42cases, the level of MGMT promoter methylaion is50%(21/42); it is in19cases that MGMT protein expresses positively, and among which5cases are methylated, so the positive expression rate is26.5%(5/19). MGMT protein expression has negative correlation with its promoter methylation.4. There is no correlation between MGMT and NF-Kb expressions (p>0.05).Conclusion:1. MGMT expression differs in grades of gliomas and it decreases as the malignancy of glioma increases.2. NF-Kb has no relation with the low or high pathological grades of gliomas.3MGMT protein expression relates closely to the MGMT promoter methylation. The level of MGMT protein expression is low when MGMT promoter is methylated, and the level is high when the MGMT promoter is demethylated.4. There is no correlation between MGMT and NF-Kb expression.