M2 macrophage marker CHI3L2 could serve as a potential prognostic and immunological biomarker in glioma by integrated single‐cell and bulk RNA‐Seq analysis

Abstract Background CHI3L2 plays a crucial role in multiple cancers, but its importance in glioma remains unclear. Hence, we comprehensively integrated bulk RNA‐sequencing (RNA‐seq), proteomics and single‐cell RNA‐seq (scRNA‐seq) to determine the roles of CHI3L2 in gliomas. Methods Bulk RNA‐seq, proteomics and scRNA‐seq data of CHI3L2 in glioma were obtained from online databases. The quantitative real‐time polymerase chain reaction (qRT‐PCR) and immunohistochemistry (IHC) were conducted to verify the CHI3L2 expression. Then, univariate and multivariate Cox regression analyses, Norman charts and gene set enrichment analysis (GSEA) were performed. Finally, the associations between CHI3L2 and tumor immunity were explored. Results The expression of CHI3L2 was markedly higher in glioma cancers compared with normal tissues from analysis of the data of the Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets and as verified by GSE4290, GSE50161, qRT‐PCR and IHC results ( p < 0.05). High expression of CHI3L2 suggested poor overall survival (OS) prognosis in gliomas ( p < 0.05). CHI3L2 might also serve as an independent predictor of OS for gliomas ( p < 0.05) and we also constructed a Norman chart to predict these patients’ survival prognosis with good performance. GSEA analysis showed that CHI3L2 might be involved with eight pathways in gliomas. Regarding tumor immunity, CHI3L2 was found to be significantly involved with immune cell infiltration levels of low‐grade glioma, the tumor immune microenvironment, immune checkpoints and immune cells in both low‐grade glioma and glioblastoma ( p < 0.05). Additionally, scRNA‐seq data for CHI3L2 in glioma from the TISCH2 website showed that CHI3L2 is mainly expressed in astrocytes, endothelial cells, CD8+ T cells, mono/macrophage cells, etc. Conclusions CHI3L2 presents prognostic and immunological values in glioma, providing novel therapeutic targets for glioma patients.