The Correlation Of MGMT Promoter Methylation And P53 Gene Mutations With The Pathological Grade In Human Brain Gliomas

Recently, as the in-depth study of the central nervous system tumors especially gliomas, there is a growing number of molecular markers to be used in human gliomas assessment and management. For example, MGMT promoter methylation, P53 gene mutation, 1p/19 q LOH, and IDH mutation such as. Researching status and relationships of these genes will help us further understand the development of gliomas, drug-resistant for tumors and malignant differentiation mechanism, and thus it also provides a theoretical basis for determining individualized treatment for gliomas.The coding gene of MGMT(O6-methylguanine-DNA-methyltransferase) located on chromosome 10q26, for encoding DNA repair proteins. It can repair damaged DNA by irreversibly transferring methyl of guanine O6 position to a cysteine residue of itself, thus reducing the cytotoxicity of temozolomide. But once it occurs MGMT promoter methylation, it will lead to reduce expression of MGMT protein, thereby inhibiting the cells’ ability of repairing DNA alkylation, allowing more effectively cytotoxicity of alkylating drugs, it can achieve better efficacy and prolong long-term survival for gliomas patients. The P53 family of transcription factors occupies an important role in the cellular response to stress in developing and homeostatic tissues. In greater than 50% of human cancers, the P53 protein is mutated or functionally inactivated. The ability of P53 to suppress tumorigenesis is fundamentally linked to its central role in the cellular response to stress. P53 potently limits the growth of damaged, potentially neoplastic cells in both embryonic and adult tissues, thus earning its moniker “guardian of the genome”.Although scholars have studied MGMT and P53 so much, these studies focused on the aspect of protein expression, while the number of clinical cases is not much and more common in foreign reports. The research is more scarce about the correlation of MGMT promoter methylation and P53 gene mutations with the pathological grade, and it is also undetermined about the exact relationships between both as well as the correlation of pathological grade, so it is particularly important for this aspect research.Objective: To discuss the correlation of MGMT promoter methylation and P53 gene mutations with the pathological grade in human gliomas.Methods: Histopathologically confirmed human gliomas tissues were collected from 132 patients including grade Ⅱ(grade Ⅰ~Ⅱ) 51 cases, grade Ⅲ 48 cases, grade Ⅳ33 cases according to WHO classification standards. It detected MGMT promoter methylation status of tumor tissue by using MSP method(methylation-specific PCR method), P53 gene mutation by using real-time quantitative PCR-HRM assay(real-time quantitative PCR-high resolution melting analysis method). By SPSS17.0 statistical software, it is compared between groups by X2 test, and correlation test was used by Spearman correlation analysis, then it was comprehensive analysis for the correlation of MGMT promoter methylation and P53 gene mutations with the pathological grade.Results:(1) In 132 cases of gliomas specimens, MGMT promoter methylation positive rate was 65.15%, the positive rate was respectively 52.94%,, 70.83%, 75.76% for grade Ⅱ(gradeⅠ~Ⅱ), grade Ⅲ and grade Ⅳ gliomas. Statistical test results showed that MGMT promoter methylation positive rate for different grade glioma was no significant difference(P>0.05, P=0.059). MGMT promoter methylation positive rate in patients with aged >50 years and ≤50 years were 64.41% and 65.75% respectively, it is no statistical difference(P > 0.05, P = 1.000); MGMT promoter methylation positive rate in male and female patients were 66.18% and 64.06% respectively, it is no statistical differences(P > 0.05, P = 0.943).(2)P53 mutation positive rate was 15.91%(21/132), the positive rate was respectively 5.88%, 14.58%, 33.33% for grade Ⅱ(gradeⅠ~Ⅱ), grade Ⅲ and grade Ⅳ gliomas. Statistical test results showed that P53 gene mutation for different grade gliomas is significant differences(P <0.05, P=0.008), the positive rate increases along with the increased grade tumor pathology. P53 mutation positive rate in patients with aged >50 years and ≤50 years were 64.41% and 65.75% respectively, it is no statistical difference(P > 0.05, P = 1.000); P53 mutation positive rate in male and female patients were 66.18% and 64.06% respectively, it is no statistical differences(P > 0.05, P = 0.745).(3)By statistical correlation analysis for MGMT promoter methylation and P53 gene mutation, suggesting that there is a positive correlation trend, but not significant(r=0.231, P= 0.008).Conclusion: By detecting MGMT promoter methylation and P53 gene mutations in 132 patients with newly diagnosed human gliomas in this study, it found a positive correlation trend, but not significant; MGMT promoter methylation status was unrelated to the patient pathological grade, while P53 gene mutations incidence will increase along with the pathological grade increased, both was unrelated to the patient’s sex and age. This conclusion is not only to provide a theoretical basis for the occur and differentiation processes of gliomas, but also has certain significance for the optimization of individual treatment with gliomas patients.