The role of IDH1 mutation on gene expression in glioblastoma

Abstract

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor found in humans. Mutations in isocitrate dehydrogenases 1 (IDH1R132H) was observed in GBM. GBMs with IDH1R132H have longer patient survival compared to GBMs with wild-type IDH1 and identifying the mechanism of this can contribute to the development of a new treatment for GBM. To investigate the role of IDH1R132H on gene expression, we incorporated three expression arrays from GEO including GSE36245, GSE131837, and GSE122586, and one expression array from TCGA which in total investigate gene expression differences between 293 wild type and 41 mutant IDH1 GBM samples. Meta-DE package in R software was applied to screen the differentially expressed genes (DEGs) between IDH1 wild type and IDH1R132H GBMs. DEGs were used to construct co-expression networks by WGCNA package for TCGA data and genes of the detected module were used to build protein-protein interaction (PPI) network. Each of the mentioned expression arrays was analyzed independently using limma package by cutoff |logFC| > 1 and P.value < 0.05, and 13 downregulated and 26 upregulated common genes were identified. By merging the results of limma package and core genes of the PPI network, 10 hub genes including ARAP3, ARHGAP11B, BDNF, CFAP45, CXCL8, MMP9, RHOBTB1, SHH, SYNJ2, and VEGFA were identified. Based on the TCGA database, we tested the prognostic significance of the detected genes using Kaplan-Meier survival analysis. In conclusion, the results suggested that the hub genes may play role in GBM pathogeny.