Objective  To investigate the role of neutrophil extracellular traps (NETs) in the pathogenesis of ulcerative colitis (UC).

Methods  RNA data from UC patients and normal controls were downloaded from the GEO database to screen for differential expression genes (DEGs), intersecting the screened genes with previously reported NETs-associated genes for functional enrichment assays such as GO, KEGG, and GSEA. Use machine learning to identify key genes for further analysis of immune infiltration and biological function. Diagnostic models were constructed based on key genes and validated against external data sets, and NETs associated molecular subtypes were identified. Prediction of drugs targeting key genes using DGIdb database.

Results  A total of 38 NETs-related DEGs were screened. F3, MME, PTAFR, and SLC25A37 were identified as key genes, with elevated levels of mRNA expression, and were associated with inflammatory signaling pathways and exhibited remarkable diagnostic efficacy. Two unique NETs-related subtypes derived from key genes had distinct immune and clinical characteristics. 22 targeted drugs might become potential therapeutic agents for UC.

Conclusion  NETs expression is elevated in UC patients and plays a pro-inflammatory role in disease progression. F3, MME, PTAFR, and SLC25A37 were identified as potential contributors to the pathogenesis of UC. The two identified subtypes of NETs can provide some reference for the clinical treatment of UC.

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