Abstract
Intervertebral disc degeneration (IDD) severely impacts patients' quality of life. Elucidating IDD's molecular mechanisms is crucial for developing effective diagnostics and therapeutics. Integrating multiple IDD gene expression datasets using bioinformatics identified 25 glycosylation-related differentially expressed genes (GRDEGs). We analyzed their biological functions and regulatory networks in IDD using GO, KEGG, GSEA, and WGCNA. An IDD diagnostic LASSO regression model was constructed and validated. Immune cell infiltration analysis using CIBERSORT/ssGSEA divided IDD samples into subtypes based on glycosylation scores, exploring the immune microenvironment's influence on heterogeneity. We explored regulatory networks involving transcription factors, miRNAs, RNA-binding proteins, and drugs affecting key genes. 25 GRDEGs were identified from 625 glycosylation-related genes (GRGs), and 9 hub genes were further screened by WGCNA to clarify their biological functions and regulatory networks. The diagnostic model based on 7 key genes performed well in the training and validation sets. In addition, Spearman correlation analysis showed that 6 key genes (MAN2B2, MAN1A1, CHI3L1, PLOD2, RAPGEF5, GLA) were significantly associated with immune cell infiltration, including Eosinophils, Dendritic cells, Macrophages M0, and T regulatory cells. Three key genes (MAN2B2, GLA, CHI3L1) significantly affected the differences between high and low glycosylation score subtypes in the immune microenvironment. In addition, regulatory networks, including 49 transcription factors, 32 miRNAs, 116 RNA-binding proteins, and 20 potential drugs, were identified. This study explored the characteristics of glycosylation-related genes in IDD and their potential association with immune infiltration, providing preliminary insights that may inform future research on diagnostic biomarkers and therapeutic targets.