Comprehensive Analysis of Core Genes, Key Pathways, and Immune Infiltration in Intervertebral Disc Degeneration Using Machine Learning and Experimental Validation

Core Genes, Pathways, and Immune Infiltration in Disc Degeneration

Abstract

Intervertebral Disc Degeneration (IVDD) is a complex biological process marked by changes in gene expression that final result in structural and functional problems in the intervertebral disc. This study was undertaken to obtain a thorough comprehension of the molecular mechanisms that drive IVDD.

The present work incorporated and examined two sets of gene expression data related to IVDD, obtained from the Gene Expression Omnibus database. An investigation of functional enrichment was conducted utilizing gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to clarify the biological processes and signaling pathways linked to these differentially expressed genes (DEGs). A protein-protein interaction (PPI) network was constructed, and Biomarkers were identified by selecting 13 hub genes using LASSO and SVM-RFE algorithms. An analysis of immune infiltration was conducted using ssGSEA, and the identification of transcription factor targets and medicines was investigated. The expression of ADM, ITGB5, RTN4, SLPI, and CSNK1E was validated using qPCR and Western blot approaches in an IL-1β-induced HNPCs model.

A profound correlation between IVDD and 112 DEGs was observed. The functional enrichment analysis demonstrated their participation in the organization of the extracellular matrix, translation in the cytoplasm, and the PI3K-Akt signaling pathway. An immunological infiltration examination revealed reduced infiltration of suppressor cells and monocytes derived from myeloid cells in the IVDD group. A total of thirteen hub genes were identified as promising indicators. An in vitro validation showed a notable decrease in the expression of ADM, ITGB5, RTN4, SLPI, and CSNK1E in the IVDD group as compared to the control group.

This thorough investigation provides deep understanding of the molecular processes that cause IVDD and reveals possible targets for treatment. The confirmation of important genes and their interactions with drugs in a laboratory setting strongly supports the results and lays the groundwork for future drug development and therapy approaches targeting IVDD.