Lipid metabolism-immune crosstalk in glioblastoma: transcriptomic associations between PLIN2, PD-L1, and CSF1

Abstract

Background: Glioblastoma is the most aggressive primary tumor of the adult central nervous system and is characterized by metabolic reprogramming and an immunosuppressive tumor microenvironment (TME) that contributes to therapeutic resistance, including limited response to immunotherapy. Evidence suggests that lipid storage, immune checkpoint signaling, and macrophage recruitment processes involving PLIN2, CD274 (PD-L1), and CSF1, respectively, may interact within this context. Objective: This study aims to investigate transcriptomic associations between lipid metabolism and immune-related processes in glioblastoma, focusing on interactions within the TME using The Cancer Genome Atlas (TCGA) data. Methods: Transcriptomic data from glioblastoma samples were obtained from the TCGA PanCancer Atlas cohort using the cBioPortal platform. All available tumor samples with RNA-seq data for the selected genes were included (n = 160). Normalized mRNA expression values (RSEM) were used, and log2 transformation [log2(value + 1)] was applied to improve data distribution and visualization. Expression levels of the lipid metabolism-related gene (PLIN2) and immune/inflammatory-related genes (CD274 and CSF1) were evaluated. Gene expression associations were assessed using scatter plots generated within the platform, and correlations were quantified using Spearman’s rank correlation coefficient. Statistical significance was defined as p < 0.05. Results: The co-expression analysis of PLIN2 and CSF1 demonstrated moderate positive correlation (Spearman’s p = 0.31; p = 8.645 × 10⁻⁵), confirming statistically significant linear associations. A weak but statistically significant positive correlation was observed between PLIN2 and CD274 expression (Spearman r ≈ 0.17, p < 0.05). A strong and statistically significant positive correlation was observed between CD274 (PD-L1) and CSF1 expression (Spearman r = 0.56, p < 0.001). Conclusion: The findings suggest a relationship between lipid metabolic reprogramming and immune related pathways in glioblastoma. The co-expression analysis of PLIN2 and CSF1 suggest potential interaction between metabolic reprogramming and remodeling of the immune environment, respectively. The analysis between PLIN2 and CD274 expression supports potential links between lipid metabolic adaptation and immune regulation within glioblastoma’s microenvironment. Finally, the observed association between CD274 and CSF1 demonstrate coordinated activation of immune checkpoint signaling and macrophage related pathways. Metabolic and immune interactions may contribute to immunosuppression in glioblastoma and could represent potential targets for further therapeutic investigation.