Identification of genes associated with cervical intervertebral disc degeneration and immune cell infiltration

This study aimed to identify novel diagnostic genetic biomarkers for early-stage cervical intervertebral disc degeneration (IDD) and to investigate the potential relationship between key genes and immune cell infiltration in IDD.

mRNA expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between cervical IDD and control samples were identified using the linear model (limma R package). Functional annotation and pathway enrichment analyses were performed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A Least Absolute Shrinkage and Selection Operator (LASSO) regression model and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) were applied to screen potential biomarkers. Immune cell composition in IDD samples was estimated using the CIBERSORT method. Cervical disc specimens were collected from patients undergoing anterior cervical discectomy and fusion (ACDF) and classified into IDD and control groups based on MRI Pfirrmann grading. Quantitative PCR (qPCR) was performed to validate biomarker expression in these specimens.

A total of 71 DEGs were identified, including 50 upregulated and 21 downregulated genes in IDD samples. KEGG pathway analysis revealed significant enrichment in inflammation-related pathways. Through machine learning screening and experimental validation, we identified CDKN3, SLC22A4, and SYDE1 as key diagnostic biomarkers for IDD. Immune infiltration analysis suggested that these genes may contribute to IDD pathogenesis by modulating specific immune cell populations. qPCR results confirmed that CDKN3 expression was significantly downregulated in cervical IDD specimens (P < 0.05), whereas SLC22A4 and SYDE1 were significantly upregulated (P < 0.05).

CDKN3, SLC22A4, and SYDE1 are associated with the pathogenesis and progression of cervical IDD, potentially through their regulatory effects on immune cell activity. These genes may serve as promising diagnostic biomarkers for cervical IDD and could aid in monitoring disease progression. Further studies are warranted to validate their clinical utility and elucidate the underlying mechanisms.