Neutrophil extracellular Trap-related genes in NAFLD: Biomarkers and therapeutic targets.

The etiology of non-alcoholic fatty liver disease (NAFLD) is complex. This study seeks to clarify the importance of neutrophil extracellular traps (NETs) -related genes in NAFLD. Integrated NAFLD datasets were obtained from GEO. NETs-related differentially expressed genes (NETsRDEGs) were identified and analyzed for functional enrichment. A diagnostic model was developed using logistic regression and Least Absolute Shrinkage and Selection Operator regression (LASSO) methods, followed by validation through receiver operating characteristic curve analysis. Immune cells infiltration assessments, regulatory network analyses, and protein domain predictions were conducted to illuminate the molecular mechanisms underlying NAFLD. We identified 22 NETsRDEGs and constructed an 8-gene diagnostic model (TLR7, LDLR, CCL2, S100A8, PADI4, F3, CD274, NFIL3) that effectively distinguished NAFLD from controls (area under the curve [AUC] = 0.920). Enrichment analyses revealed significant involvement of PI3K-AKT signaling and negative regulation of NOTCH4 signaling. Immune infiltration analysis demonstrated altered abundances of activated CD8 + T cells and Type 2 T helper in NAFLD. Several compounds, including resveratrol and curcumin, were identified as potential therapeutics. Our findings underscore the significance of NETs in NAFLD pathogenesis, involving inflammatory pathways and immune dysregulation. The identified NETsRDEGs and diagnostic model offer promising biomarkers and therapeutic avenues for NAFLD.