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

ABSTRACT:

SUBMITTER: Chen W

PROVIDER: S-EPMC11209862 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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

Project description: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.

2023-06-30 | GSE234762 | GEO