ORIGINAL RESEARCH article
Front. Oncol.
Sec. Neuro-Oncology and Neurosurgical Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1573997
This article is part of the Research TopicInnovative Strategies in Overcoming Glioblastoma: Advancements in Treatment and ResearchView all 4 articles
Integrative Analysis of Crotonylation-Associated Genes Reveals Prognostic and Therapeutic Targets in Gliomas
Provisionally accepted
- Fudan University, Shanghai, China
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Background: Crotonylation, an emerging epigenetic modification, has been implicated in various biological processes, including tumor progression.However, its role in glioma remains poorly understood. This study aims to investigate the prognostic and therapeutic implications of crotonylationassociated genes in glioma.Methods: Crotonylation levels were assessed by IHC in glioma tissues of varying grades. Key crotonylation-associated genes were identified and analyzed across five glioma datasets. A prognostic risk score was developed using machine learning algorithms and validated in multiple cohorts. Genomic alterations, immune landscapes, and therapeutic responses were examined in relation to the risk score. Single-cell dataset GSE131928 was analyzed to explore the relationship between the risk score and immune cell infiltration.After crotonate treatment of T98G cells, ChIP-seq and qPCR were performed to investigate the effect of crotonylation on gene expression. Finally, PD-1 and GZMB expression levels were assessed in glioma tissues with varying crotonylation levels.Results: Crotonylation levels were negatively correlated with glioma grade.Crotonylation-related genes stratified patients into two subtypes with distinct overall survival outcomes. High-risk patients exhibited increased somatic mutations, specific copy number variations, and an immunosuppressive tumor microenvironment. The risk score correlated positively with TIDE scores, indicating resistance to immune checkpoint blockade therapy. Single-cell analysis revealed a positive association between the risk score and TAM infiltration. Candidate therapeutic agents tailored for high-and low-risk groups were identified. ChIP-seq and qPCR demonstrated that reduced crotonylation suppressed CXCL1 expression and promoted GZMB expression in the glioma microenvironment.Crotonylation-associated genes play a pivotal role in glioma progression and prognosis. The risk score provides a robust tool for patient stratification and treatment guidance, underscoring the importance of crotonylation in glioma biology and its potential as a therapeutic target.
Keywords: Glioma, Tumor Microenvironment, prognosis, machine learning, ChIP-seq, CXCL1
Received: 10 Feb 2025; Accepted: 09 Jun 2025.
Copyright: © 2025 Yin, Fan, Yu, Li, Wang and Shu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yilin Wang, Fudan University, Shanghai, China
Minfeng Shu, Fudan University, Shanghai, China
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