Bioinformatics Analysis and Identification of Ferroptosis-Related Hub Genes in Intervertebral Disc Degeneration.

Approximately 80% of individuals encounter lower back pain (LBP), a prevalent clinical issue largely attributed to intervertebral disc degeneration (IDD). Ferroptosis is an iron-dependent lipid peroxidation-driven cell death, and there is growing evidence that ferroptosis plays an important role in various human diseases. However, the underlying mechanism of ferroptosis in IDD remains unclear. This study aims to reveal the potential hub genes and related pathways of ferroptosis in the pathogenesis and progression of IDD. In this study, we analyzed three microarray datasets from the GEO database. Additionally, we downloaded ferroptosis-related genes from FerrDb-V2 and extracted apoptosis-related genes from UniProt as a control to show the specificity of ferroptosis. Weighted gene co-expression network analysis (WGCNA) was performed to identify the IDD-related module genes. Then, ferroptosis-related genes and apoptosis-related genes were separately overlapped with the IDD-related module genes, resulting in the identification of 35 ferroptosis-related module genes (FRMG) and 142 apoptosis-related module genes (ARMG). Furthermore, we performed functional enrichment analysis and protein-protein interaction network, and Cytoscape along with CytoHubba was used to identify the hub genes. Finally, logistic regression models were constructed and identified two hub FRMGs (PTEN and EGFR) and one hub ARMG (CTNNB1), which could distinguish IDD patients from controls (P < 0.05). The areas under the ROC curves were 0.792 and 0.730, respectively, suggesting that ferroptosis is more specific than apoptosis in IDD. In conclusion, this study provided fresh perspectives on ferroptosis in the pathogenesis and progression of IDD that can be used to evaluate potential biomarker genes and therapeutic targets.