Immune heterogeneity and clinicopathologic characterization of IGFBP2 in 2447 glioma samples.

ABSTRACT

Glioblastoma is an immunosuppressive, deadly brain tumor. IGFBP2, a circulating biomarker for cancer diagnosis and a potential immunotherapeutic target, is attracting more and more attention from oncologists and clinicians. Thus, it is urgent to thoroughly investigate the immune biological process of IGFBP2 to understand tumor immune complexity and provide potential evidence for anti-IGFBP2 therapy. Through authoritative public databases, we enrolled a total of 2447 glioma samples with gene expression profiles. Then, the clinical characteristics and immunosuppressive status of IGFBP2 in the glioma samples were analyzed. Immunohistochemical staining detected the expression of immunosuppressive biomarkers. We found that IGFBP2 expression was upregulated in high-grade glioma and GBM and downregulated in IDH mutant glioma. Increased IGFBP2 accompanied PTEN loss and EGFR amplification. Bioinformatic analysis revealed that IGFBP2 is related to immunological processes. We further selected specific immunologic related gene sets and found IGFBP2 predominated immunosuppressive activities in GBM. Furthermore, we explored the relationship between IGFBP2 and genes that were well-characterized glioma-mediated immunosuppressive molecules to investigate the potential effect of IGFBP2. We discovered that IGFBP2 was correlated with CHI3L1, TNFRSF1A, LGALS1, TIMP1, VEGFA, ANXA1 and LGALS3, which were classic immunosuppressive biomarkers. Higher IGFBP2 expression predicted unfavorable survival for patients with GBM. Our findings implied that IGFBP2 is involved in immunosuppressive activities and is an independent unfavorable prognostic biomarker for patients with GBM. IGFBP2 is a potential immunotherapeutic target for GBM in future clinical trials.