Bioinformatics analysis identifies IL-23A and JAK2 as regulatory factors in sepsis immune response via the JAK/STAT3...

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Identifying key genes associated with sepsis and exploring their interactions with immune cells are crucial for advancing diagnostic and therapeutic strategies.

In order to explore the genetic underpinnings, five datasets-GSE28750, GSE57065, GSE64457, GSE65682, and GSE95233-were analyzed using the "Limma" package in R to identify differentially expressed genes (DEGs). Functional enrichment analysis was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-protein interaction (PPI) networks and key modules were analyzed using STRING and Cytoscape. The core genes were selected using the least absolute shrinkage and selection operator (LASSO) regression, and their diagnostic value was validated through receiver operating characteristic (ROC) curve analysis. Immune cell infiltration was assessed using the CIBERSORT algorithm.

A total of 230 DEGs were identified, including 183 upregulated and 47 downregulated genes. GO and KEGG analysis revealed significant enrichment in immune-related pathways. Two core genes, IL-23A and JAK2, emerged as key players. ROC curve analysis demonstrated high diagnostic value with area under the curve (AUC) values of 0.82 and 0.90 for IL-23A and JAK2, respectively. IL-23A showed a strong positive correlation with CD8+ T cells and activated natural killer (NK) cells, while also activating the JAK/STAT3 signaling pathway and mitigating JAK2-mediated immune cell infiltration.

This study highlights the potential role of IL-23A and JAK2 in the immune regulation of sepsis and provides new insights into immune therapeutic strategies via the JAK/STAT3 signaling pathway.