Ten genes associated with MGMT promoter methylation predict the prognosis of patients with glioma.

Abstract

Glioma originates from the glial cells of the spine or brain, and promoter methylation of O6-methylguanine-DNA methyltransferase (MGMT) can promote the chemosensitivity of glioma. The present study aimed to reveal the key genes implicated in MGMT promoter methylation in patients with glioma. RNA-sequencing data and methylation data for glioma were extracted from The Cancer Genome Atlas database. Following expression characteristic analysis and differential expression analysis using unsupervised hierarchical clustering and a rank sum test, the feature genes were identified between high and low methylation groups. Furthermore, multivariate survival analysis for the feature genes was performed using the survival package in R. Additionally, the independent glioma RNA expression datasets GSE7696 and GSE42669 were used to validate the prognostic efficiency of the gene combination. The results indicated that the prognosis of the low methylation group was significantly worse than that of the high methylation group. The ten genes corresponding to the cut-off value of 0.56 (Rho GTPase-activating protein 21, CECR2, histone acetyl-lysine reader, endosulfine α, G-patch domain-containing 8, KIAA1109, MGMT, protocadherin β 13, selenoprotein M, sperm-associated antigen 9 and WD repeat domain 6) were able to significantly predict prognosis and were differentially expressed between the two groups. Multivariate survival analysis suggested that the ten genes were effective for sample classification and prognostic prediction. Furthermore, the validation datasets confirmed the correlation of the ten genes with prognosis. In conclusion, these 10 genes may be mediated by MGMT promoter methylation in glioma. In addition, the ten-gene combination may be associated with the prognosis of patients with glioma.