Integrative Analysis of CBR1 As a Prognostic Factor Associated with IDH-mutant Glioblastoma in the Chinese Population

Overview

Journal Am J Transl Res

Specialty General Medicine

Date 2022 Sep 15

PMID 36105052

Authors

Pengxiang Ji

Xueshi Shan

Jian Wang

Ping Zhang

Zhan Cai

Affiliations

Soon will be listed here.

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.

Citing Articles

Robust Cluster Prediction Across Data Types Validates Association of Sex and Therapy Response in GBM.

Gibbs D, Cioffi G, Aguilar B, Waite K, Pan E, Mandel J Cancers (Basel). 2025; 17(3).

PMID: 39941811 PMC: 11815886. DOI: 10.3390/cancers17030445.

Single cell sequencing revealed the mechanism of CRYAB in glioma and its diagnostic and prognostic value.

Cai H, Zhao M, Li X, Li Y, Yu T, Wang C Front Immunol. 2024; 14:1336187.

PMID: 38274814 PMC: 10808695. DOI: 10.3389/fimmu.2023.1336187.

References

May J, Kouri F, Hurley L, Liu J, Tommasini-Ghelfi S, Ji Y . IDH3α regulates one-carbon metabolism in glioblastoma. Sci Adv. 2019; 5(1):eaat0456. PMC: 6314828. DOI: 10.1126/sciadv.aat0456. View

Witthayanuwat S, Pesee M, Supaadirek C, Supakalin N, Thamronganantasakul K, Krusun S . Survival Analysis of Glioblastoma Multiforme. Asian Pac J Cancer Prev. 2018; 19(9):2613-2617. PMC: 6249474. DOI: 10.22034/APJCP.2018.19.9.2613. View

Liu X, Yamaguchi K, Takane K, Zhu C, Hirata M, Hikiba Y . Cancer-associated IDH mutations induce Glut1 expression and glucose metabolic disorders through a PI3K/Akt/mTORC1-Hif1α axis. PLoS One. 2021; 16(9):e0257090. PMC: 8437293. DOI: 10.1371/journal.pone.0257090. View

Flavahan W, Drier Y, Liau B, Gillespie S, Venteicher A, Stemmer-Rachamimov A . Insulator dysfunction and oncogene activation in IDH mutant gliomas. Nature. 2015; 529(7584):110-4. PMC: 4831574. DOI: 10.1038/nature16490. View

Zhao Z, Zhang K, Wang Q, Li G, Zeng F, Zhang Y . Chinese Glioma Genome Atlas (CGGA): A Comprehensive Resource with Functional Genomic Data from Chinese Glioma Patients. Genomics Proteomics Bioinformatics. 2021; 19(1):1-12. PMC: 8498921. DOI: 10.1016/j.gpb.2020.10.005. View

Chen J, Tong X, Han M, Zhao S, Ji L, Qin Y . Cost-Effectiveness of Short-Course Radiation Plus Temozolomide for the Treatment of Newly Diagnosed Glioblastoma Among Elderly Patients in China and the United States. Front Pharmacol. 2021; 12:743979. PMC: 8502816. DOI: 10.3389/fphar.2021.743979. View

Horbinski C, Kelly L, Nikiforov Y, Durso M, Nikiforova M . Detection of IDH1 and IDH2 mutations by fluorescence melting curve analysis as a diagnostic tool for brain biopsies. J Mol Diagn. 2010; 12(4):487-92. PMC: 2893633. DOI: 10.2353/jmoldx.2010.090228. View

Xu Q, Wang K, Wang L, Zhu Y, Zhou G, Xie D . IDH1/2 Mutants Inhibit TET-Promoted Oxidation of RNA 5mC to 5hmC. PLoS One. 2016; 11(8):e0161261. PMC: 4993491. DOI: 10.1371/journal.pone.0161261. View

Pei G, Chen L, Zhang W . WGCNA Application to Proteomic and Metabolomic Data Analysis. Methods Enzymol. 2017; 585:135-158. DOI: 10.1016/bs.mie.2016.09.016. View

10.

Zhou L, Yang C, Zhong W, Wang Q, Zhang D, Zhang J . Chrysin induces autophagy-dependent ferroptosis to increase chemosensitivity to gemcitabine by targeting CBR1 in pancreatic cancer cells. Biochem Pharmacol. 2021; 193:114813. DOI: 10.1016/j.bcp.2021.114813. View

11.

Krell D, Assoku M, Galloway M, Mulholland P, Tomlinson I, Bardella C . Screen for IDH1, IDH2, IDH3, D2HGDH and L2HGDH mutations in glioblastoma. PLoS One. 2011; 6(5):e19868. PMC: 3100313. DOI: 10.1371/journal.pone.0019868. View

12.

Eckel-Passow J, Lachance D, Molinaro A, Walsh K, Decker P, Sicotte H . Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors. N Engl J Med. 2015; 372(26):2499-508. PMC: 4489704. DOI: 10.1056/NEJMoa1407279. View

13.

Al-Qusairi L, Prokic I, Amoasii L, Kretz C, Messaddeq N, Mandel J . Lack of myotubularin (MTM1) leads to muscle hypotrophy through unbalanced regulation of the autophagy and ubiquitin-proteasome pathways. FASEB J. 2013; 27(8):3384-94. DOI: 10.1096/fj.12-220947. View

14.

Zhou S, Cao H, Zhao Y, Li X, Zhang J, Hou C . RACK1 promotes hepatocellular carcinoma cell survival via CBR1 by suppressing TNF-α-induced ROS generation. Oncol Lett. 2017; 12(6):5303-5308. PMC: 5228530. DOI: 10.3892/ol.2016.5339. View

15.

Oldrini B, Vaquero-Siguero N, Mu Q, Kroon P, Zhang Y, Galan-Ganga M . MGMT genomic rearrangements contribute to chemotherapy resistance in gliomas. Nat Commun. 2020; 11(1):3883. PMC: 7403430. DOI: 10.1038/s41467-020-17717-0. View

16.

Barracco V, Moschini R, Renzone G, Cappiello M, Balestri F, Scaloni A . Dehydrogenase/reductase activity of human carbonyl reductase 1 with NADP(H) acting as a prosthetic group. Biochem Biophys Res Commun. 2019; 522(1):259-263. DOI: 10.1016/j.bbrc.2019.11.090. View

17.

Oliveira A, Anjo S, Vieira de Castro J, Serra S, Salgado A, Manadas B . Crosstalk between glial and glioblastoma cells triggers the "go-or-grow" phenotype of tumor cells. Cell Commun Signal. 2017; 15(1):37. PMC: 5625790. DOI: 10.1186/s12964-017-0194-x. View

18.

Coughlin 2nd C, Tseng L, Abdenur J, Ashmore C, Boemer F, Bok L . Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to α-aminoadipic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis. 2020; 44(1):178-192. DOI: 10.1002/jimd.12332. View

19.

Nakae S, Murayama K, Sasaki H, Kumon M, Nishiyama Y, Ohba S . Prediction of genetic subgroups in adult supra tentorial gliomas by pre- and intraoperative parameters. J Neurooncol. 2016; 131(2):403-412. DOI: 10.1007/s11060-016-2313-8. View

20.

Li X . Identification of key genes for laryngeal squamous cell carcinoma using weighted co-expression network analysis. Oncol Lett. 2016; 11(5):3327-3331. PMC: 4840875. DOI: 10.3892/ol.2016.4378. View