Cancer-associated fibroblast-associated gene IGFBP2 promotes glioma progression through induction of M2 macrophage polarization

Abstract

We elucidated the molecular mechanism of Cancer-associated fibroblasts (CAF)-associated gene IGFBP2-induced M2 macrophage polarization in the tumor microenvironment involved in glioma progression. TCGA and CGGA provided bulk RNA-seq datasets, ESTIMATE scores for glioma stromal cells, and OS-clinicopathological correlation analyses. TIMER provided CAF abundance in the TCGA glioma-related dataset, differential gene analysis was performed for high and low CAF groups, and weighted gene co-expression network analysis (WGCNA) identified CAF-related genes. Univariate and multifactorial COX regression analyses created CAF risk models. ssGSEA, CIBERSORT, GSE84465. Implanted glioma mice finished. Western blot and RT-qPCR showed IGFBP2 in tumor tissues. AAV decreased IGFBP2, flow cytometry measured M1 and M2 macrophage ratios, and immunohistochemistry detected markers. TCGA and CGGA transcriptome data showed malignant gliomas had higher stromal cell scores and worse prognoses. Low- and high-CAF TCGA gliomas. Differential expression, WGCNA, and multifactorial COX identified 132 CAF-related genes and 7 high-risk genes (CPQ, EFEMP2, IGFBP2, RAB42, TNFRSF12A, VASN). Neither CAF risk score, Grade, nor 1p/19q affected glioma prognosis. CAF only enriched EFEMP2 and IGFBP2. GEPIA compared EFEMP2 and IGFBP2 expression in normal brain tissue and gliomas. LGG and GBM highly expressed IGFBP2 and EFEMP2. GSEA raised IGFBP2. CIBERSORT linked M2 macrophage infiltration to TCGA glioma immune cell subpopulation IGFBP2 expression. IGFBP2 knockdown stopped mouse glioma and M2 macrophage polarization. CAF plays a pro-carcinogenic role in glioma, and the CAF-related gene IGFBP2 could promote glioma progression by inducing M2 macrophage polarization.