ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1660754
This article is part of the Research TopicInnovative Strategies in Overcoming Glioblastoma: Advancements in Treatment and ResearchView all 10 articles
The Role of Immune-and Lipid Metabolism-Related Genes in Macrophage Polarization and Prognosis of Glioblastoma
Provisionally accepted
- Department of Neurosurgery, Shanghai Ninth People’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Objective: To investigate the roles of immune-and lipid metabolism-related genes in macrophage polarization and their prognostic and therapeutic implications in glioblastoma (GBM). Methods: A total of 655 GBM samples from The Cancer Genome Atlas (TCGA) were stratified into immune and non-immune groups based on immune scores. Differentially expressed genes (DEGs) were identified, and their intersection with 859 lipid metabolism–related genes yielded 26 candidates. A 10-gene prognostic signature was constructed using univariate and least absolute shrinkage and selection operator (LASSO) Cox regression analyses and validated in both internal (TCGA) and independent (Chinese Glioma Genome Atlas, CGGA) cohorts. Functional enrichment, single-cell transcriptomic analysis, experimental validation, and drug sensitivity profiling were performed to assess the biological and therapeutic relevance of the identified genes. Results: Ten immune-and lipid metabolism–related genes were significantly associated with GBM prognosis. Key genes such as LGALS1, PLA2G5, and FABP5 were upregulated in high-risk patients and enriched in M2-like tumor-associated macrophages. Enrichment analyses indicated their involvement in immune regulation and lipid metabolic pathways. Their elevated expression in GBM tissues was confirmed by qRT-PCR and Western blot. Drug sensitivity analysis demonstrated a correlation between LGALS1 expression and the response to agents such as zoledronate and staurosporine. Conclusions: Immune-and lipid metabolism–related genes contribute to macrophage polarization and are closely linked to GBM prognosis. The identified gene signature provides prognostic value and potential therapeutic targets for immunometabolic modulation in GBM.
Keywords: Glioblastoma1, macrophage polarization2, lipid metabolism3, prognostic genes4, Immune response5
Received: 06 Jul 2025; Accepted: 23 Sep 2025.
Copyright: © 2025 Zhang, Xu, Li, Liao, Xiaosheng and Zhang. 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:
Yang Xiaosheng, jupiter1985@126.com
Wenchuan Zhang, zhangwench88@hotmail.com
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