Impact of ferroptosis-related risk genes on macrophage M1/M2 polarization and prognosis in glioblastoma
- PMID: 38283752
- PMCID: PMC10817728
- DOI: 10.3389/fncel.2023.1294029
Impact of ferroptosis-related risk genes on macrophage M1/M2 polarization and prognosis in glioblastoma
Abstract
Objective: To explore the effect impact of ferroptosis on macrophage polarization and patient prognosis in glioblastoma.
Methods: We screened ferroptosis-related risk from the public datasets of primary and recurrent glioblastoma, combined with reported ferroptosis genes, calculated the risk genes among the ferroptosis-related genes using the LASSO Cox regression model, and investigated the relationship between these ferroptosis-related risk genes in the tumor and the spectrum of infiltrating M1/M2 macrophages. Macrophages were analyzed using the CIBERSORTx deconvolution algorithm. Samples from The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA) and a single-cell RNA sequencing dataset (GSE84465) were included. The expression levels of ferroptosis-related risk genes and molecular markers of M1 and M2 macrophages were detected by qPCR and western blot.
Results: A total of fourteen ferroptosis-related risk genes were obtained and the patients' risk scores were calculated. Compared with patients in the low-risk group, patients in the high-risk group had worse prognosis. The M1/M2 macrophage ratio and risk score were negatively correlated, indicating that the tumor microenvironment of glioblastoma in the high-risk group contained more M2 than M1 macrophages. In the single-cell RNA sequencing dataset, the risk score of ferroptosis-related genes in tumor cells was positively correlated with the proportion of high M2 macrophages. The expression of eight ferroptosis-related risk genes was increased in glioblastoma cell, which promoted the polarization of M1 macrophages to M2.
Conclusion: We investigated the fourteen ferroptosis-related risk genes in glioblastoma for the first time, and clarified the impact of ferroptosis-related risk genes on M1/M2 macrophage polarization and patient prognosis.
Keywords: M1/M2 macrophages; ferroptosis; glioblastoma; macrophage polarization; prognosis.
Copyright © 2024 Xu, Zhang, Liao, Zhou, Wu and Zhang.
Conflict of interest statement
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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