IL8 associated with M2 macrophage infiltration as a prognostic biomarker differentiates WHO grade III and grade IV gliomas

Abstract

Abstract Malignant glioma can be divided into grade III (Gr. III) and grade IV (Gr. IV). Gr. III glioma patients have significantly better overall survival (OS) than those with Gr. IV glioma, also known as glioblastoma multiforme (GBM). We explored differentially expressed genes (DEGs) from the GSE4290 and GSE109857 datasets between Gr. III and Gr. IV gliomas. Six candidate prognostic genes for GBM were determined from survival analysis of data obtained from The Cancer Genome Atlas (TCGA), and the results were validated via assessments of the OS of Gr. III glioma and GBM patients using data obtained from the Chinese Glioma Genome Atlas (CGGA). Then, the expression levels of CXCL8, also named IL8, had a significant relationship with progression-free survival (PFS) in Gr. IV patients (P = 0.028), and had no effect in Gr. III glioma patients (P = 0.522). Furthermore, the receiver operating characteristic (ROC) curve revealed the critical role of IL8 with an accuracy value of 0.899 for discriminating Gr. IV from Gr. III in TCGA and 0.644 in CGGA. Macrophage (P < 0.001) and neutrophil (P < 0.001) levels were highly related to IL8 levels, especially for M2 macrophage markers. All M2 markers increased the correlative efficiency from primary GBM to the recurrence group. IL8 in GBM has a significant effect on disease prognosis and tumor immunity. IL8-associated M2 macrophage infiltration could be a prognostic biomarker used to classify GBM and Gr. III gliomas.