Decoding Septic Shock Genetics: Immune Pathway Disruption and Target Discovery

Recent advancements in understanding the pathogenesis and therapeutic approaches for septic shock have been made; however, research elucidating genetic-level mechanisms remains limited. This study aims to explore genetic contributors to septic shock pathogenesis and evaluate differentially expressed genes as potential diagnostic targets. Utilizing the GSE95233 dataset from the GEO database, we compared blood samples from 51 septic shock patients and 22 healthy controls via R language and GEO2R tools. We identified 38 differentially expressed genes (21 upregulated, 17 downregulated). GO functional enrichment analysis of differential genes was carried out using the Cluster Profiler package in R language, and the results showed that most of the differential genes were distributed in T cells, which were related to the development, differentiation, recognition, and clearance of T cells, and the regulation of inflammatory cytokines, which directly affected immune signaling and immune killing pathways. We also analyzed the interaction network between differentially expressed proteins with the help of string online website and MCODE plug-in in Cytoscape 3.8.2, and identified 9 core genes, including BCL11B and TBX21 genes related to immune cell development and differentiation, CD247, CD3G, CD8A and S1PR5 genes related to T cell signaling, PRF1 and GNLY genes related to immune cell killing activity. Through the evaluation of gene function and the prediction of the mechanism of action, we determined that BCL11B, TBX21, S1PR5, CD247, PRF1 and other differential genes can be used as new targets for research to prevent the exacerbation of sepsis and treat septic shock.