Identification of diagnostic biomarkers related to the efferocytosis pathway and immune cell infiltration characteristics in pediatric sepsis by bioinformatics analysis

Pediatric sepsis is a serious disease characterized by multiple organ failure. Due to its unique pathogenesis, its clinical mortality rate is very high. This study systematically evaluated the value of efferocytosis related genes in the diagnosis of sepsis in children. We downloaded gene expression profiles related to pediatric sepsis from the gene expression omnibus database, identify differentially expressed genes (DEGs) by limma R package, and retrieve adult sepsis gene expression profiles to determine the specificity of pediatric sepsis biomarkers. Selected pediatric sepsis specific genes from these profiles and used clusterProfiler for Kyoto Encyclopedia of Genes and Genomes (KEGG), gene ontology, and Reactome databases for functional enrichment. Genesets related to Efferocytosis was searched in the KEGG database, and the intersection with pediatric sepsis specific genes was considered as pediatric sepsis-efferocytosis genes. Immune infiltration analysis was performed using the CIBERSORT package. Constructed a protein-protein interaction (PPI) network and screened for hub genes in pediatric sepsis-efferocytosis genes. Further select diagnostic markers through gene expression and receiver operating characteristic (ROC) curve. We identified a total of 281 DEGs specific to pediatric sepsis, which are enriched in pathways such as phagosome, autophagy and efferocytosis. We found that the efferocytosis pathway is significantly up-regulated in pediatric sepsis, while this pathway is not significant in adult sepsis. We noticed that 12 types of immune cells infiltration levels including macrophages in pediatric sepsis patients. We selected the top 20 hub genes with PPI network. By overlapping hub genes with pediatric sepsis-efferocytosis genes, we obtained 2 hub pediatric sepsis-efferocytosis genes (ALOX5, CD36). The ROC curve suggested that these genes may be potential diagnostic markers for pediatric sepsis. We have identified ALOX5 and CD36 as efferocytosis related genes associated with pediatric sepsis, which can reliably identify pediatric sepsis and provide prospective clinical references for the pathogenesis of pediatric sepsis.