Gene expression profiling and the isocitrate dehydrogenase mutational landscape of temozolomide-resistant glioblastoma

Glioblastoma(GBM), an aggressive brain cancer, occurs frequently compared to other brain tumors. This study aimed to reveal the novel mechanism of temozolomide (TMZ) resistance (chemotherapeutic drug) Meta-Z analysis, Kaplan–Meier (KM) survival analysis, protein-protein interaction (PPI) network establishment, cluster analysis of co-expressed gene networks, and hierarchical clustering of all upregulated and downregulated genes were used. Next-generation sequencing (NGS) and quantitative polymerase chain reaction (q-PCR) analysis revealed the downregulated (TIE1, CACNA2D1, CAPN6, and ADAMTS6) and upregulated (SAA1, SAA2, GDF15, and USP26) genes. Different statistical models were developed for these genes using the Z-score and the KM plot was depicted using a cohort of patient with brain tumors. The maximum number of nodes was observed in the PPI-network for ADAMTS6 and TIE1. The PPI network model of all genes showed 35 nodes and 241 edges. Immunohistochemical staining was performed using GBM with isocitrate dehydrogenase (IDH)-wild-type or IDH-mutant samples and significant upregulation of TIE1 (p<0.001) and CAPN 6 (p<0.05) protein expression was found in IDH-mutant GBM. Structural analysis revealed the IDH-mutant model using mutant residues (R132, R140, and R172). The result of this study will aid the development of novel biomarkers and new therapeutics for brain tumors. To investigate rarely discussed RNAs, it includes messenger RNA (mRNA) and long non-coding RNAs (lincRNA), which related to chemotherapeutic-resistant GBM. We generated a TMZ-resistant GBM8401 cell line, which is through 140 days of continuous 200 μM TMZ-treatment, to simulate GBM chemotherapeutic resistance. We performed gene expression profiling analysis using data obtained from RNA-seq of two different cells. Comparative gene expression profiling analysis of RNA-seq for GBM8401 cells and TMZ-resistant GBM8401 cell line.