Integrative analysis of CBR1 as a prognostic factor associated with IDH-mutant glioblastoma in the Chinese population

Am J Transl Res. 2022 Aug 15;14(8):5394-5408. eCollection 2022.

Abstract

Background: Glioblastoma multiforme (GBM) is a common primary intracranial tumor with poor prognosis. Common indicators in the clinical diagnosis of glioma include MGMT promoter methylation, isocitrate dehydrogenase (IDH) mutation, 1p/19q codeletion, and TERT mutation. Among these, IDH mutation is extremely important for GBM diagnosis and treatment.

Methods: The Chinese Glioma Population Database (CGGA) and Gene Expression Omnibus (GEO) data (GSE131273) related to glioma in the Chinese population were used for differential analysis (DGA) and weighted gene coexpression network analysis (WGCNA). The expression levels of hub genes between the IDH1 wild-type and mutant GBM cell lines were detected by RT-qPCR. Kaplan-Meier (KM) plotter was used to analyze hub gene expression levels and prognostic values.

Results: Eight hub genes were identified by WGCNA and different expression genes (DEG) analysis, namely, one upregulated gene (CRYAB) and seven downregulated genes (EFEMP2, RBP1, TAGLN2, CBR1, MSN, ALDH7A1, and MT1M). Four of these genes (ALDH7A1, MSN, CBR1, and MTM1) showed significant differences between IDH-wild-type and IDH-mutant GBM, verified at the cellular level. Moreover, the high expression of CBR1 was significantly correlated with poor overall survival (OS) in patients with IDH-mutant GBM, and we finally identified CBR1 as a specific prognostic factor in IDH-mutant GBM.

Conclusion: Results revealed different gene expressions between IDH-wild-type and IDH-mutant GBM. These genes may help monitor the occurrence and development of glioma. CBR1 can be used as a prognostic marker to identify IDH-mutant glioblastoma patients.

Keywords: GBM; IDH mutation; WGCNA; differential analysis; prognostic marker.