Identification and Verification of Potential Core Genes in Pediatric Septic Shock

Abstract

Background: Septic shock is a frequent and costly problem among patients in the pediatric intensive care unit (PICU) and is associated with high mortality and devastating survivor morbidity. In this study, we aimed to screen candidate biomarkers and potential therapeutic targets for septic shock. Methods: GSE26440 dataset was downloaded from Gene Expression Omnibus (GEO), including 32 normal controls and 98 children with septic shock RNA samples from whole blood. The pathways and functional annotations of differentially expressed genes (DEGs) in the two types of samples were examined by GO and KEGG pathway enrichment analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Protein-protein interactions (PPI) of the above-described DEGs were investigated using the Search Tool for the Retrieval of Interacting Genes (STRING) and Hub gene identification was performed by the plug-in cytoHubba in Cytoscape software. Results: A total of 140 genes were identified as DEGs, of which 98 genes were up-regulated and 42 genes were down-regulated. GO function analysis showed that DEGs were significantly enriched in biological processes, including immune response, leukocyte activation involved in immune response, and so on. The top hub genes, namely MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, S100A12, GPR97, and TRAT1 were recognized from the protein-protein interaction (PPI) network. Furthermore, qRT-PCR results demonstrated that the mRNA level of MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, and S100A12 was elevated while GPR97 was decreased in involved mouse and human models. However, TRAT1 expression is species-dependent which was decreased in the mouse septic shock model but elevated in the human LPS-treated macrophages model. Conclusion: Taken together, the identification and validation of several novel hub genes, especially GPR97 and TRAT1, deepen our comprehension of the molecular mechanisms of septic shock progression. These genes may be therapeutic molecular targets or diagnostic biomarkers in patients with septic shock.