Integrative Multi-Omics and Single-Cell Profiling Identify Chitinase Domain Containing Protein 1 (CHID1) as a...

Glioblastoma multiforme (GBM), the most aggressive primary brain tumor, is characterized by high recurrence, metabolic plasticity, and complex tumor microenvironmental interactions. The human chitinase and chitinase-like protein family includes five members (CHI3L1, CHI3L2, CHIA, CHID1, and CHIT1) that share conserved chitinase-related domains but exhibit diverse biological functions in immune regulation and tissue remodeling. While chitinase-like proteins are recognized as mesenchymal-associated markers, however, the role of CHID1 in GBM remains largely unexplored. An integrative multi-omics strategy combining TCGA-GBM and CGGA transcriptomic datasets, single-cell RNA sequencing, and enrichment analyses (GSEA, GO, KEGG, and MetaCore) were used to investigate CHID1 expression patterns and associated transcriptional programs. Pharmacogenomic correlations and molecular docking were used to explore potential drug-response associations. CHID1 showed higher expression in GBM compared to the normal brain and was associated with poor overall survival. A single-cell analysis showed tumor-associated expression patterns of CHID1 across malignant samples. Pathway enrichment analyses identified transcriptional programs related to oxidative phosphorylation, redox-related processes, DNA repair, and cell cycle pathways. Collectively, this study provides a comprehensive multi-cohort and multi-modal characterization of CHID1 expression in GBM, integrating bulk transcriptomics, single-cell RNA sequencing, and tissue-level validation. The findings establish CHID1 as a GBM-associated transcriptional marker linked to metabolic and redox-related programs and provide a systematic resource for future investigations into chitinase family-related biology in GBM.