Identification of Genes Associated with Disulfidptosis in the Subacute Phase of Spinal Cord Injury and Analysis of Potential Therapeutic Targets

Shenglong Wang¹Xiaochen Su¹Wenting Xu²Yonghui Zhao¹Yulong Zhang¹Yingang Zhang^1*

• ¹The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
• ²Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China

This study systematically identified core regulatory genes associated with disulfidptosis during the subacute phase of spinal cord injury (SCI) using bioinformatics approaches, and explored potential therapeutic targets and candidate compounds. Two GEO datasets, GSE151371 (human) and GSE45006 (rat) were analyzed. A total of 6,948 differentially expressed genes (DEGs) were identified from GSE151371, and intersected with known disulfidptosis-related genes (DRGs) to obtain 8 disulfidptosis-related DEGs (DE-DRGs). CIBERSORT was employed to assess immune cell infiltration, while small molecule prediction and molecular docking were used to screen candidate regulatory compounds. Key diagnostic genes were further identified using random forest and LASSO algorithms, and their discriminative power evaluated by ROC curves. A protein–protein interaction (PPI) network was constructed via the STRING database to assess regulatory centrality. Mfuzz time-series clustering of GSE45006 was performed to analyze the dynamic expression patterns of DE-DRGs. Among them, IQGAP1 was significantly upregulated in SCI samples, positively correlated with neutrophil infiltration, and located at the center of the PPI network. It was selected as a key feature gene by both machine learning algorithms, with an AUC of 0.974. Molecular docking indicated strong binding affinity between IQGAP1 and small molecules such as vitamin E (binding energy < −7.0 kcal/mol). Time-series analysis showed that IQGAP1 expression markedly increased on day 7 post-injury and remained elevated throughout the subacute phase. Functional enrichment analyses (GO, KEGG, GSVA, GSEA) suggested its involvement in cytoskeleton remodeling, immune regulation, and metabolic reprogramming. Immunofluorescence in SCI rat models confirmed consistent spatial expression and functional potential. In summary, IQGAP1 is a core regulator of disulfidptosis in subacute SCI, exhibiting both diagnostic value and therapeutic potential, and represents a promising target for secondary injury intervention.