Cuproptosis-Related Biomarkers and Characterization of Immune Infiltration in Sepsis.

Abstract

Sepsis is a worldwide epidemic, with high morbidity and mortality.Cuproptosis is a form of cell death that is associated with a wide range of diseases. This study aimedto explore genes associated withcuproptosisin sepsis, construct predictive modelsandscreen for potential targets. The LASSO algorithm and SVM-RFE model has been analysedthe expression ofcuproptosis-related genes in sepsis and immune infiltration characteristics and identified the marker genes under a diagnostic model. Gene-drug networks, mRNA-miRNA networksandPPI networks were constructed to screen for potential biological targets. The expression of marker genes was validated based on the GSE57065 dataset. Consensus clustering method was used to classify sepsis samples. We found 381 genes associated with the development of sepsis anddiscovered significantly differentially expressedcuproptosis-related genes of 16 cell types in sepsis and immune infiltration with CD8/CD4 T cells being lower.NFE2L2, NLRP3, SLC31A1, DLD, DLAT, PDHB, MTF1, CDKN2A andDLST were identified as marker genes by the LASSO algorithm and the SVM-RFE model. AUC > 0.9 was constructed for PDHB and MTF1 alone respectively. The validation group data for PDHB (P=0.00099) and MTF1 (P=7.2e-14) were statistically significant. Consistent clustering analysis confirmed two subtypes.The C1 subtype may be more relevant to cellular metabolism and the C2 subtype has some relevance to immune molecules.The results of animal experiments showed that the gene expression was consistent with the bioinformatics analysis. Our study systematically explored the relationship between sepsis andcuproptosisand constructed a diagnostic model. And, severalcuproptosis-related genes may interfere with the progression of sepsis through immune cell infiltration.