CD36 as a potential prognostic biomarker and modulator of the tumor microenvironment in glioma

Cluster of differentiation 36 (CD36) is functioning as a fatty acid transporter, which is implicated in tumor progression. However, whether the pathophysiological functions of CD36 are associated with the prognosis of glioma is still relatively unknown. This study aimed to explore the potential role of CD36 in glioma and to clarify its potential as a possible therapeutic target for glioma.

Gene expression profiles and clinical data of glioma patients were obtained from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. Patients were stratified into high- and low-expression groups for survival assessment. Cox proportional hazards regression models were applied to evaluate the association between CD36 expression levels and overall survival (OS), including both univariate and multivariate analyses. U87, U251, and LN229 glioma cell lines were subjected to CD36 knockdown using small interfering RNA (siRNA). Cell proliferation was measured by the colony formation, Cell Counting Kit-8 (CCK-8), and EdU assays. The migration ability was evaluated by Transwell and wound healing assays. To explore potential biological functions, differentially expressed genes (DEGs) were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Immune cell infiltration in the tumor microenvironment (TME) was quantified by Estimate, CIBERSORT, and ssGSEA algorithms, with a focus on macrophages and neutrophils. CD36 mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR), and correlation analyses were performed to investigate associations between CD36 expression and immune cell infiltration.

High expression of CD36 was associated with unfavorable clinicopathological features in glioma patients and may indicate poor prognosis. A prognostic model constructed based on CD36 expression, age, World Health Organization (WHO) grade, isocitrate dehydrogenase (IDH) status, and 1p/19q codeletion status showed good predictive performance for glioma patient outcomes. In vitro, CD36 promoted glioma cell proliferation and migration, thereby contributing to tumor progression. CD36 played an important role in shaping the immune microenvironment of gliomas; its overexpression enhanced the infiltration of myeloid-derived macrophages and neutrophils, leading to an immunosuppressive TME.

CD36 not only serves as a vital biomarker for predicting prognosis and monitoring glioma progression, but also plays a pivotal role in reshaping the TME of glioma. Specifically, CD36 contributes to the development of an immunosuppressive TME, underscoring its significance in the progression of glioma.