Mitophagy-Oxidative Stress Molecular Subtypes Define an Immunosuppressive Ecosystem and Vulnerabilities in Glioblastoma.

Overview

1. Beijing Chaoyang Hospital, The Third Clinical Medical College Capital Medical University Beijing China
2. Department of Neurosurgery, Beijing Chaoyang Hospital Capital Medical University Beijing China

Abstract

Glioblastoma (GBM) is an aggressive brain tumour with an immunosuppressive environment and poor prognosis; however, the roles of mitophagy and oxidative stress in its prognosis remain underexplored. This study analysed multi‐omics data from TCGA‐GBM (n = 168) and two GEO cohorts (GSE43378, n = 50; GSE147352, n = 85), compiling 603 mitophagy and oxidative stress‐related genes. Unsupervised consensus clustering identified molecular subtypes, and prognostic genes were found via univariate Cox regression, leading to a refined gene signature using LASSO. The tumour immune microenvironment was characterized with ESTIMATE, CIBERSORT, and ssGSEA, while immunotherapy response was predicted using TIDE and IPS. Drug sensitivity was evaluated with GDSC and CTRP data, and a clinical nomogram integrating the gene signature and clinical variables was constructed and validated. Two molecular subtypes, C1 and C2, showed different prognoses (HR = 0.64, p = 0.011) and immune profiles. A 7‐gene signature indicated high‐risk patients had worse survival (p < 0.001) and an immunosuppressive environment. The risk score correlated with anti‐PD‐1 response (p < 0.05) and predicted therapy sensitivity. The signature was an independent prognostic factor (HR = 3.37, p < 0.001), and the nomogram accurately predicted survival at 1, 3, and 5 years. An innovative prognostic signature from mitophagy and oxidative stress genes stratifies GBM patients, characterizes the immunosuppressive microenvironment, and identifies therapeutic vulnerabilities for personalized treatment.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Data links

• ncbi.nlm.nih.gov/geo — NCBI; found in “Data Availability Statement”

Data Availability Statement

The original datasets analysed in this study are publicly available. The transcriptomic and clinical data for the TCGA‐GBM cohort can be accessed via the Genomic Data Commons (GDC) portal (https://portal.gdc.cancer.gov/) under the project ‘TCGA‐GBM’. The validation datasets GSE43378 and GSE147352 are available from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) under the accession numbers GSE43378 and GSE147352, respectively. The mitophagy and oxidative stress‐related gene (MORG) list, the derived 7‐gene signature, and the analysis codes supporting the findings of this study are available from the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 3 authors, 5 keywords, 11 MeSH terms, 55 references.

Cite

This paper

He, C., Wang, Y., & Zhong, H. (2026). Mitophagy-Oxidative Stress Molecular Subtypes Define an Immunosuppressive Ecosystem and Vulnerabilities in Glioblastoma. Journal of cellular and molecular medicine, 30(10), e71154. https://doi.org/10.1111/jcmm.71154

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