Associations between NETosis-related genes and 28-day mortality in patients with sepsis: An observational retrospective study and bioinformatic analysis

ObjectiveSepsis, a systemic inflammatory response triggered by infection, is characterized by organ dysfunction. NETosis, a form of cell death involving the release of neutrophil extracellular traps (NETs), plays a crucial antimicrobial role during sepsis. This study aimed to explore the relationship between NETosis-related genes (NRGs) and 28-day mortality in patients with sepsis.MethodsThis retrospective observational study utilized the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Univariate and multivariate logistic regression analyses were conducted to identify independent prognostic factors. A nomogram was then constructed to assess the potential of these factors in predicting 28-day mortality in patients with sepsis. Additionally, a Mendelian randomization (MR) study was performed to identify NRGs with causal associations to 28-day mortality in sepsis. Expression validation was carried out using the GSE65682 dataset from a public database, followed by identification of key genes. Enrichment analysis was performed to uncover the molecular mechanisms associated with these key genes in sepsis.ResultsA total of 909 patients with sepsis (706 survivors and 203 non-survivors) were identified from the MIMIC-IV database. Seven independent prognostic factors, including absolute neutrophil counts, were identified. The nomogram developed proved to be a reliable tool for predicting 28-day mortality in patients with sepsis. The MR study identified 12 NRGs with a unidirectional causal relationship to 28-day mortality, with AKT1 and CXCR2 emerging as key genes. Both genes are predominantly involved in immune-related pathways.ConclusionAnalysis of the MIMIC-IV database highlighted neutrophil_abs as a significant prognostic factor for 28-day mortality in sepsis. Transcriptomic analysis identified AKT1 and CXCR2 as critical genes associated with 28-day mortality, providing insights into potential therapeutic strategies for sepsis.