ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1586921
This article is part of the Research TopicAdvancing Glioma Treatment: Novel Drugs, Mechanisms of Resistance, and Therapeutic StrategiesView all 11 articles
Palmitoylation-Driven Immune Dysregulation and Prognostic Signature in low-grade glioma: A Multi-Omics and Functional Validation Study
Provisionally accepted
- 1School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China
- 2Department of Urology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China
- 3Tianjin University of Traditional Chinese Medicine, Tianjin, China
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Background: Palmitoylation, a critical post-translational modification, regulates protein localization and function in cancer. However, its role in glioma progression, immune modulation, and prognosis remains poorly understood.Methods: We integrated transcriptomic, clinical, and mutation data from multicenter cohorts to analyze 30 palmitoylation-related genes in low-grade gliomas (LGG). Consensus clustering, differential expression analysis, and LASSO regression were employed to define palmitoylation clusters, identify prognostic genes, and construct a risk signature. The evaluation of immune infiltration and immunotherapy efficacy was further conducted across different risk groups. In the palmitoylation-related risk model, IGFBP2 was functionally validated through siRNA-mediated knockdown and a series of assays, including EdU incorporation, cell cycle analysis, wound healing, and transwell migration assays.Results: Two palmitoylation clusters (A/B) were identified, with Cluster B exhibiting poorer survival (P < 0.001), enriched JAK-STAT signaling, and elevated immune infiltration (M1/M2 macrophages, CD8+ T cells). A five-gene prognostic signature (CHI3L1, IGFBP2, MEOX2, EMILIN3, SFRP2) demonstrated robust predictive accuracy in training (AUC 0.92-0.94) and validation cohorts (AUC 0.68-0.83). High-risk patients showed upregulated PD-1, PD-L1, and CTLA4 (P < 0.001) and higher TIDE scores, indicative of immune dysfunction.IGFBP2 knockdown suppressed glioma cell proliferation (P < 0.01) and migration (P < 0.001), linking it to tumor aggressiveness.Conclusion: Palmitoylation plays a pivotal role in LGG progression by influencing immune evasion and stromal interactions. The developed prognostic signature and nomogram offer practical tools for risk stratification in clinical settings, with IGFBP2 identified as a promising therapeutic target. These insights highlight the potential of palmitoylation-focused therapies to enhance outcomes for LGG patients.
Keywords: palmitoylation, LGG, Prognostic signature, Tumor Microenvironment, Immune infiltration, IGFBP2, Immunotherapy
Received: 03 Mar 2025; Accepted: 15 May 2025.
Copyright: © 2025 Wang, Wu and Hu. 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:
Yufan Wu, Department of Urology, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China
Jingqing Hu, Tianjin University of Traditional Chinese Medicine, Tianjin, China
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