The Clinical Value Of MGMT Autoantibodies Directed Against Glioblastoma Chemotherapy

Objective: MGMT gene encodes a full-length cDNA sequences of 769bp, which containing an open reading frame of 621bp and encoding 207 amino acids, its molecular weight is 22ku, the active site is in cysteine residue 145, The alkyl at the O6-position of guanine on the DNA molecule can be catalyzed by MGMT unconditionally and transferred to its cysteine residue 145, this makes guanine damage repair, DNA structure and function recovery, while MGMT irreversibly inactivated after the turn-methyl. now we have not found other proteins involved in this process, it is this principle so that TMZ chemotherapy failure. Our study is based on polypeptide microarray technology to explore the value of MGMT autoantibodies in guiding chemotherapy on glioblastoma patients.Methods:In 28 cases of human glioma tissues, including 20 cases Glioblastoma multiforme (GBM) and 8 cases astrocytoma, and another 4 cases of normal human brain tissues for the study, polypeptide microarray technology were used to detect MGMT autoantibodies in response to the polypeptides, methylation-specific polymerase chain reaction(MSP) to detect MGMT gene promoter methylation status, immunohistochemistry(IHC) to detect the expression of MGMT protein.Results:28 cases of glioma specimens,9 cases of MGMT autoantibodies in response to polypeptide,19 cases did not respond, the response rate was 32.1%; MGMT gene promoter methylation in 10 cases,18 cases unmethylation; 14 cases of positive expression of MGMT,14 cases negative. In 4 cases of normal brain tissues, MGMT autoantibodies do not respond to polypeptide, the promoter region are unmethylation, protein expression were negative. In 20 cases of GBM patients, MGMT autoantibody was positively correlated with promoter methylation status(r=0.579, p<0.01); The expression of MGMT protein was negatively correlated with promoter methylation status(r=-0.533, p<0.05).Conclusions:Preliminary determination, maybe there is no MGMT autoantibody in the serum of normal people, but MGMT autoantibodies in glioma patients do respond to polypeptide. In 20 cases of GBM patients, there is a significant correlation of MGMT polypeptide microarrays and IHC results and MSP results, polypeptide microarray for detecting MGMT atuoantibodies have certain effect on the prediction of resistance to TMZ in GBM patients, to determine the sensitivity of GBM patients with TMZ by detecting MGMT autoantibodies, not only to solve the blind chemotherapy on patients due to the inability to obtain tumor tissue for molecular and pathological examination, but also to determine whether the patients with secondary appeared resistant to TMZ in the chemotherapy process.