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. Overall design: 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.