Multi-omics Analysis Revealed that the CCN Family Regulates Cell Crosstalk, Extracellular Matrix, and Immune Escape, Leading to a Poor Prognosis of Glioma

The CCN family is a group of matricellular proteins associated with the extracellular matrix. This study aims to explore the role of the CCN family in glioma development and its implications in the tumor microenvironment. Through analysis of bulk RNA-seq cohorts, correlations between CCN family expression and glioma subtypes, patient survival, and bioactive pathway enrichment were investigated. Additionally, single-cell datasets were employed to identify novel cell subgroups, followed by analyses of cell communication and transcription factors. Spatial transcriptomic analysis was utilized to validate the CCN family’s involvement in glioma. Results indicate overexpression of CYR61,CTGF, and WISP1 in glioma, associated with unfavorable subtypes and reduced survival. Enrichment analyses revealed associations with oncogenic pathways, while CTGF and WISP1 expression correlated with increased infiltration of regulatory T cells and M2 macrophages. Single-cell analysis identified MES-like cells as the highest CCN expression. Moreover, intercellular signal transduction analysis demonstrated active pathways, including SPP1-CD44, in cell subgroups with elevated CYR61 and CTGF expression. Spatial transcriptomic analysis confirmed co-localization of CYR61,CTGF and SPP1-CD44 with high oncogenic pathway activity. These findings suggest that CCN family members may serve as potential prognostic biomarkers and therapeutic targets for glioma.