Identifying pyroptosis- and inflammation-related genes in spinal cord injury based on bioinformatics analysis

Spinal cord injury (SCI) is a common traumatic central nervous system disorder characterized by a complex microenvironment after injury, leading to severe neurological dysfunction. Increasing attention has been paid to the role of inflammatory cells in SCI. Pyroptosis, a form of programmed inflammatory cell death, plays a significant role in SCI; however, its underlying mechanisms remain unclear. This study utilized bioinformatics methods to identify pyroptosis-related genes (PRGs) and investigate their roles in inflammatory responses. Additionally, we explored the potential interactions between differentially expressed PRGs (DEPRGs) and miRNAs(microRNAs), lncRNAs(Long non-coding RNAs), and circRNAs(Circular RNAs). RNA expression profiles, including mRNA(Messenger RNA), miRNA, lncRNA, and circRNA, were obtained from the Gene Expression Omnibus (GEO) database. A total of 78 PRGs were identified through a literature search in PubMed. DEPRGs, miRNAs, lncRNAs, and circRNAs were screened using R software. Functional enrichment analyses of DEPRGs were performed, and a protein-protein interaction (PPI) network was constructed. Weighted Gene Co-expression Network Analysis (WGCNA) was conducted, and external validation was performed using an independent dataset to identify hub genes and their correlations with immune cells. Western blotting was used to validate hub gene expression. Finally, a competing endogenous RNA (ceRNA) network was constructed based on differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs), and circRNAs (DEcircRNAs). Eleven DEPRGs were identified in SCI, including ten upregulated and one downregulated gene. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DEPRGs were mainly enriched in processes such as the regulation of interleukin-1 beta production, NLRP3 inflammasome complex, and NOD-like receptor signaling pathway. Two hub genes, IL18 and GSDMD, were identified using Cytoscape and WGCNA. External dataset validation revealed significant differences in hub gene expression between SCI and control groups (P < 0.05), with AUC(Area Under Curve) values > 0.75. Immune infiltration analysis indicated significant positive correlations between hub genes and M1 macrophages, CD8 + T cells, and resting dendritic cells. Four downregulated DEmiRNAs were identified as potential regulators of hub genes. Additionally, 29 DEmiRNAs, 55 upregulated DElncRNAs, and 2 upregulated DEcircRNAs were identified and used to construct the ceRNA network. Bioinformatics analyses revealed a strong association between pyroptosis and SCI, identifying two potential hub genes, IL18 and GSDMD, linked to pyroptosis and immune cell infiltration. These findings provide insights into the potential mechanisms of pyroptosis in SCI and offer a basis for further studies.