Abstract
BACKGROUND: Peroxisomes are vital organelles involved in metabolic processes such as fatty acid metabolism and reactive oxygen species detoxification. Their role in sepsis, characterized by systemic inflammation and organ dysfunction, is not well understood. This study focuses on pediatric sepsis, utilizing gene expression profiles from pediatric sepsis patients and healthy controls. METHODS: We analyzed differentially expressed peroxisome-related genes (DPGs) using the GSE26378 dataset. ssGSEA assessed peroxisome pathway activity, immune cell infiltration, and immune-related pathways, examining their relationships. Key marker genes were identified using LASSO, RF, and Logistic Regression. A nomogram was constructed to predict sepsis risk based on these markers. An in vivo animal model of LPS-induced sepsis was also utilized to validate the expression of key marker genes (EPHX2 and IDH1). RESULTS: Sixteen DPGs were identified in sepsis. Peroxisome pathway activity was significantly increased in the sepsis group, positively correlating with neutrophils and macrophages, and negatively with NK cells. In sepsis, pathways related to immunity, inflammation, and apoptosis were activated, with a strong positive correlation between peroxisome activity and these pathways. Machine learning algorithms revealed key marker genes, EPHX2 and IDH1, validated through the GSE13904 and GSE26440 datasets, and LPS-induced animal experiments. CONCLUSION: Our findings underscore the significant role of peroxisome-related processes in sepsis, particularly their interaction with immune dynamics and pathways. The identified marker genes may serve as potential therapeutic targets, by linking immune infiltration to peroxisomal gene expression, enhancing our understanding of sepsis pathophysiology and improving clinical outcomes.