Differential Expression of Disulfidptosis-Related Genes in Spinal Cord Injury and Their Role in the Immune Microenvironment.

Spinal cord injury (SCI) often results in severe sensory, motor, and autonomic dysfunction, with limited treatment options due to complex underlying mechanisms. Disulfidptosis, a recently discovered form of cell death driven by disulfide bond accumulation, has been linked to various diseases, but its role in SCI remains unexplored. This study investigates the involvement of disulfidptosis-related genes (DRGs) in SCI to identify potential diagnostic markers and therapeutic targets. Using SCI datasets from the Gene Expression Omnibus (GEO), we conducted differential gene expression analysis, identifying key disulfidptosis-related differentially expressed genes (DRDEGs). Further analysis through gene set enrichment (GSEA) and Bayesian pathway enrichment highlighted significant involvement in pathways such as NF-κB, PI3K/Akt, and MAPK, with an emphasis on nephrin family interactions. Three core DRDEGs-HK2, Map3k8, and S100a6-were identified, and a diagnostic model built on these genes demonstrated strong predictive performance (AUC: 0.896 in training, 0.850 in validation). Additionally, real-time PCR (qRT-PCR) in an animal model validated the elevated expression of these DRDEGs in SCI samples. This research provides novel insights into disulfidptosis in SCI, suggesting these genes as promising targets for improved diagnostic and therapeutic strategies.