Identification and Analysis of Biomarkers Associated With Lipid Metabolism and Ferroptosis in Ulcerative Colitis.

BACKGROUND

Mounting evidence shows that lipid metabolism and ferroptosis contribute to ulcerative colitis (UC), but the mechanism remains unclear. This study aimed to identify related biomarkers, clarify their roles in UC, and provide insights into optimized therapies.

METHODS

UC transcriptome, lipid metabolism, and ferroptosis-related gene (FRG) data were analyzed. Biomarkers were screened via differential expression analysis, consensus clustering, Venn, and machine learning, with expression validation. Receiver operating curve (ROC) analysis assessed predictive efficacy; functional enrichment, molecular regulatory, and immune infiltration analyses were performed. Real-time PCR verified candidate biomarkers in clinical samples.

RESULTS

Two biomarkers (acyl-CoA synthetase ligases 4 [ACSL4] and prostaglandin-endoperoxide synthase 2 [PTGS2]) were identified that distinguished UC from control samples. They may involve hematopoietic cell lines, cytokine-cytokine receptor interaction, and MALAT1 binding hsa-miR-576-5p/hsa-miR-503-5p. Notably, 27 differentially infiltrated immune cells were found (p  < 0.05), with CD56dim natural killer cells negatively correlating with ACSL4/PTGS2. Both genes were significantly upregulated in the UC clinical samples.

CONCLUSION

ACSL4 and PTGS2 are lipid metabolism- and ferroptosis-related biomarkers of UC, laying a foundation for clinical treatment.