M2 macrophage infiltration associated with CXCL8 predicts grade 4 prognosis and differentiates glioma grades.

BACKGROUND: This study aims to improve glioma-WHO grading by identifying biomarkers distinguishing Gr. 4 from Gr. 3 gliomas and exploring their immune-related prognostic significance. METHODS: We analyzed differentially expressed genes (DEGs) between Gr. 3 and Gr. 4 gliomas using the GSE4290 (31 Gr. 3, 77 Gr. 4) and GSE109857 (34 Gr. 3, 89 Gr. 4) datasets. Key genes were identified through protein-protein interaction (PPI) network and KEGG pathway enrichment analyses. These genes underwent survival analysis and validation using data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA). RESULTS: Among 23 key genes, CXCL8/IL8 and THBS1 were validated in TCGA and CGGA datasets. CXCL8 significantly correlated with progression-free survival (PFS) in Gr. 4 gliomas (p = 0.028) but not Gr. 3 (p = 0.522). ROC analysis confirmed its diagnostic accuracy (AUC: 0.899 in TCGA, 0.644 in CGGA). Immune infiltration analysis linked CXCL8 to macrophages (p < 0.001) and neutrophils (p < 0.001), particularly M2 macrophages. CONCLUSIONS: CXCL8 has a significant impact on disease prognosis and tumor immunity in Gr. 4 gliomas. The association of CXCL8 with M2 macrophage infiltration suggests that CXCL8-related markers could serve as potential prognostic biomarkers for differentiating between Gr. 4 and Gr. 3 gliomas.