Construction and validation of a cuproptosis-related prognostic model for glioblastoma

BackgroundCuproptosis, a newly reported type of programmed cell death, takes part in the regulation of tumor progression, treatment response, and prognosis. But the specific effect of cuproptosis-related genes (CRGs) on glioblastoma (GBM) is still unclear.MethodsThe transcriptome data and correspond...

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Main Authors: Bohong Zhang, Lin Xie, Jiahao Liu, Anmin Liu, Mingliang He
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-02-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1082974/full
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author Bohong Zhang
Lin Xie
Jiahao Liu
Anmin Liu
Mingliang He
author_facet Bohong Zhang
Lin Xie
Jiahao Liu
Anmin Liu
Mingliang He
author_sort Bohong Zhang
collection DOAJ
description BackgroundCuproptosis, a newly reported type of programmed cell death, takes part in the regulation of tumor progression, treatment response, and prognosis. But the specific effect of cuproptosis-related genes (CRGs) on glioblastoma (GBM) is still unclear.MethodsThe transcriptome data and corresponding clinical data of GBM samples were downloaded from the TCGA and GEO databases. R software and R packages were used to perform statistical analysis, consensus cluster analysis, survival analysis, Cox regression analysis, Lasso regression analysis, and tumor microenvironment analysis. The mRNA and protein expression levels of model-related genes were detected by RT-qPCR and Western blot assays, respectively.ResultsThe expression profile of CRGs in 209 GBM samples from two separate datasets was obtained. Two cuproptosis subtypes, CRGcluster A and CRGcluster B, were identified by consensus cluster analysis. There were apparent differences in prognosis, tumor microenvironment, and immune checkpoint expression levels between the two subtypes, and there were 79 prognostic differentially expressed genes (DEGs). According to the prognostic DEGs, two gene subtypes, geneCluster A and geneCluster B, were identified, and a prognostic risk score model was constructed and validated. This model consists of five prognostic DEGs, including PDIA4, DUSP6, PTPRN, PILRB, and CBLN1. Ultimately, to improve the applicability of the model, a nomogram was established. Patients with GBM in the low-risk cluster have a higher mutation burden and predict a longer OS than in the high-risk group. Moreover, the risk score was related to drug sensitivity and negatively correlated with the CSC index.ConclusionWe successfully constructed a cuproptosis-related prognostic model, which can independently predict the prognosis of GBM patients. These results further complement the understanding of cuproptosis and provide new theoretical support for developing a more effective treatment strategy.
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spelling doaj.art-ab5bdeab6d0a43a498edb5a60069686f2023-02-06T05:23:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.10829741082974Construction and validation of a cuproptosis-related prognostic model for glioblastomaBohong Zhang0Lin Xie1Jiahao Liu2Anmin Liu3Mingliang He4Department of Anesthesiology, the Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, ChinaDepartment of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaDepartment of Neurosurgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, ChinaBackgroundCuproptosis, a newly reported type of programmed cell death, takes part in the regulation of tumor progression, treatment response, and prognosis. But the specific effect of cuproptosis-related genes (CRGs) on glioblastoma (GBM) is still unclear.MethodsThe transcriptome data and corresponding clinical data of GBM samples were downloaded from the TCGA and GEO databases. R software and R packages were used to perform statistical analysis, consensus cluster analysis, survival analysis, Cox regression analysis, Lasso regression analysis, and tumor microenvironment analysis. The mRNA and protein expression levels of model-related genes were detected by RT-qPCR and Western blot assays, respectively.ResultsThe expression profile of CRGs in 209 GBM samples from two separate datasets was obtained. Two cuproptosis subtypes, CRGcluster A and CRGcluster B, were identified by consensus cluster analysis. There were apparent differences in prognosis, tumor microenvironment, and immune checkpoint expression levels between the two subtypes, and there were 79 prognostic differentially expressed genes (DEGs). According to the prognostic DEGs, two gene subtypes, geneCluster A and geneCluster B, were identified, and a prognostic risk score model was constructed and validated. This model consists of five prognostic DEGs, including PDIA4, DUSP6, PTPRN, PILRB, and CBLN1. Ultimately, to improve the applicability of the model, a nomogram was established. Patients with GBM in the low-risk cluster have a higher mutation burden and predict a longer OS than in the high-risk group. Moreover, the risk score was related to drug sensitivity and negatively correlated with the CSC index.ConclusionWe successfully constructed a cuproptosis-related prognostic model, which can independently predict the prognosis of GBM patients. These results further complement the understanding of cuproptosis and provide new theoretical support for developing a more effective treatment strategy.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1082974/fullcuproptosisprognosistumor microenvironmentrisk score modelglioblastoma
spellingShingle Bohong Zhang
Lin Xie
Jiahao Liu
Anmin Liu
Mingliang He
Construction and validation of a cuproptosis-related prognostic model for glioblastoma
Frontiers in Immunology
cuproptosis
prognosis
tumor microenvironment
risk score model
glioblastoma
title Construction and validation of a cuproptosis-related prognostic model for glioblastoma
title_full Construction and validation of a cuproptosis-related prognostic model for glioblastoma
title_fullStr Construction and validation of a cuproptosis-related prognostic model for glioblastoma
title_full_unstemmed Construction and validation of a cuproptosis-related prognostic model for glioblastoma
title_short Construction and validation of a cuproptosis-related prognostic model for glioblastoma
title_sort construction and validation of a cuproptosis related prognostic model for glioblastoma
topic cuproptosis
prognosis
tumor microenvironment
risk score model
glioblastoma
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1082974/full
work_keys_str_mv AT bohongzhang constructionandvalidationofacuproptosisrelatedprognosticmodelforglioblastoma
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AT jiahaoliu constructionandvalidationofacuproptosisrelatedprognosticmodelforglioblastoma
AT anminliu constructionandvalidationofacuproptosisrelatedprognosticmodelforglioblastoma
AT minglianghe constructionandvalidationofacuproptosisrelatedprognosticmodelforglioblastoma