ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicRegulatory Mechanisms of Post-Translational Modifications in Cancer MetabolismView all articles
Comprehensive analysis of palmitoylation-related proteins for prognostic risk evaluation and tumor immune microenvironment assessment in glioma
Provisionally accepted
- 1Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- 2Department of Center for Renal Diseases, Sichuan Provincial People's Hospital East Sichuan Hospital & Dazhou First People's Hospital, Dazhou, Sichuan, China., Dazhou, China
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Glioma is one of the most common tumors, characterized by a high incidence rate and mortality, posing a formidable global health challenge. Palmitoylation represents a significant post-translational modification that holds a pivotal role in the progression of glioma. However, the biological mechanisms underlying palmitoylation-related genes (PRGs) in glioma remain elusive to date. In this study, two palmitoylation-related subtypes were distinguished in glioma patients based on palmitoylation-related genes. We showed significant differences in clinicopathological characteristics, immune features, and prognostic stratification between the two clusters. Based on the LASSO Cox regression analysis, we developed a palmitoylation-related risk score (PRRS) model and validated its predictive value in immunotherapy in the TCGA-GBM LGG, CGGA_325, CGGA_301, and CGGA_693 datasets. We observed a significant correlation between PRRS and factors including age, WHO grade, IDH mutation, 1p/19q codeletion, and MGMT promoter methylation status. Moreover, a nomogram was formulated to facilitate the clinical application of PRRS, with its accuracy and validity confirmed through diverse methodologies. We undertook a comprehensive drug sensitivity analysis, alongside molecular docking and molecular dynamics simulations, to forecast potential small molecule compounds targeting palmitoylation-related proteins, and we also conducted experimental validation on these drugs. Drawing upon these findings, we can deduce that a significant correlation exists between palmitoylation and tumor microenvironment in glioma. Furthermore, the PRRS emerges as a dependable prognostic biomarker, offering therapeutic advantages in the context of chemotherapy and immunotherapy, and potentially aiding in clinical decision-making for glioma patients. The identified compounds, AT-7519, BIX02189, and THZ-2-101-1, may potentially exert inhibitory effects on the malignant progression of glioma by targeting palmitoylation-related proteins.
Keywords: Glioma, palmitoylation, Tumor immune microenvironment, risk score, Immunotherapy, Methylation
Received: 25 Mar 2025; Accepted: 18 Nov 2025.
Copyright: © 2025 Xue, Yin, Wang, Lai, Wang and Chen. 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: Ligang Chen, chengligang.cool@163.com
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