Identification of Immune-Related Key Genes as Potential Diagnostic Biomarkers of Sepsis in Children

Abstract

Objective The pathogenesis of sepsis is still unclear due to its complexity, especially in children. This study aimed to analyse the immune microenvironment and regulatory networks related to sepsis in children at the molecular level and to identify key immune-related genes to provide a new basis for the early diagnosis of sepsis. Methods The GSE145227 and GSE26440 datasets were downloaded from the Gene Expression Omnibus. The analyses included differentially expressed genes (DEGs), functional enrichment, immune cell infiltration, the competing endogenous RNA (ceRNA) interaction network, weighted gene coexpression network analysis (WGCNA), protein–protein interaction (PPI) network, key gene screening, correlation of sepsis molecular subtypes/immune infiltration with key gene expression, the diagnostic capabilities of key genes, and networks describing the interaction of key genes with transcription factors and small-molecule compounds. Finally, real-time quantitative PCR (RT–qPCR) was performed to verify the expression of key genes. Results A total of 236 immune-related DEGs, most of which were enriched in immune-related biological functions, were found. Further analysis of immune cell infiltration showed that M0 macrophages and neutrophils infiltrated more in the sepsis group, while fewer activated memory CD4 + T cells, resting memory CD4 + T cells, and CD8 + T cells did. The interaction network of ceRNA was successfully constructed. Six key genes (FYN, FBL, ATM, WDR75, FOXO1 and ITK) were identified by WGCNA and PPI analysis. We found strong associations between key genes and constructed septic molecular subtypes or immune cell infiltration. Receiver operating characteristic analysis showed that the area under the curve values of the key genes for diagnosis were all greater than 0.84. Subsequently, we successfully constructed an interaction network of key genes and transcription factors/small-molecule compounds. Finally, the key genes in the samples were verified by RT–qPCR. Conclusion Our results offer new insights into the pathogenesis of sepsis in children and provide new potential diagnostic biomarkers for the disease.

Identification of qualitative characteristics of immunosuppression in sepsis based on immune-related genes and immune infiltration features

“…Compared to previous studies, our work introduces a novel approach for the early diagnosis of sepsis by employing an REO-based algorithm. Lu et al [ 14 ] utilized modified Lasso penalized regression and Random Forest to construct an IRG classifier, and Wang et al [ 54 ] focused on pediatric sepsis using various bioinformatics analyses; our study is the first to identify three immune-related gene pairs using an REO-based algorithm. Additionally, unlike Peng et al [ 20 ], whose focus was on predicting 28-day mortality in patients with sepsis, our study aimed at early diagnosis in a broader population with a substantially larger sample size.…”

Identification and verification of feature biomarkers associated with immune cells in neonatal sepsis

“…Sepsis is characterized by upregulation of CD4 + and CD8 + T cells, T helper 17 cells, and regulatory T cells [ 16 ], lymphopenia, and loss of immune function. Microarray analysis has indicated abnormalities in the expression of immune-related genes in children with sepsis, including FYN, FBL, ATM, WDR75, FOXO1, and ITK [ 18 ]. Alterations in gene expression related to innate immunity have also been reported in NS [ 19 , 20 ].…”

The Presence of PDL-1 on CD8+ Lymphocytes Is Linked to Survival in Neonatal Sepsis

“…While most commonly accepted measures were highly variable and did not change significantly, there were changes in CD8 + T cells and a clear significant downward trend in deceased children. The level of CD8 + lymphocytes is a rare and variable finding among sepsis biomarkers; however, CD8 + T cells were previously described to play a key role in mice [ 23 ] and as a biomarker of early neonatal sepsis [ 24 , 25 , 26 ]. In particular, Carey et al [ 27 ] reported that the number of unique T cell receptors is limited during the first trimester.…”