Integrated Bioinformatics Analysis Identifies and Validates Novel Cellular Senescence-Associated Genes in Sepsis and Sepsis-Induced ARDS

Abstract Sepsis can lead to acute respiratory distress syndrome (ARDS) and is associated with a high mortality rate. This study investigated cellular senescence-related genes in sepsis and sepsis-induced ARDS to identify novel biomarkers. Using bioinformatics analyses including WGCNA and machine learning on public datasets, six hub genes (NFIL3, GARS, PIGM, DHRS4L2, CLIP4, LY86) were identified. These genes showed strong diagnostic value and were associated with immune cell infiltration and key pathways. Validation in lipopolysaccharide (LPS)-stimulated neutrophils showed significant upregulation of NFIL3. The findings highlight the role of cellular senescence in pathogenesis and identify promising therapeutic targets for sepsis-induced ARDS.