Identification of a Novel Ferroptosis-Associated Gene Signature of Ulcerative Colitis

Abstract

Background: Ulcerative colitis (UC) is a widely known form of inflammatory bowel disease (IBD), and its main symptoms include colonic and rectal inflammation. This research focused on the identification of key genes associated with UC ferroptosis and the development of novel biomarkers for the disease. Methods: Gene set variation analyses (GSVA) were used to calculate the enrichment score (ES) of the ferroptosis-related gene set in each sample in GSE38713 and GSE47908, respectively. Subsequently, to obtain key modules, the ES were used as traits for subsequent weighted gene co-expression network analysis (WGCNA), and finally, to obtain key genes, the genes in the two modules were intersected. Biomarker screening was performed by building a protein-protein interaction (PPI) network of key genes, where the top 20 hub genes were screened using the Cytoscape. In addition, the receiver operating characteristic (ROC) curve was drawn for the selected hub genes, and the top-ranked hub genes were screened out for the diagnosis of ulcerative colitis. To assess the diagnostic value, the validation dataset GSE87466 was applied to draw ROC curves for the candidate hub genes. Results: GSVA revealed that the ferroptosis gene set had a strong association with UC. WGCNA was used to obtain 2636 significant genes in GSE38713. WGCNA was used to obtain 3512 significant genes in GSE47908. Intersection analysis of the two yielded 604 intersection genes. In addition, in the protein-protein interaction (PPI) network, 20 hub genes of intersection genes were identified using the Cytoscape. Finally, receiver operating characteristic analysis of selected hub genes revealed that four genes were the potential ferroptosis-associated genes for UC. Conclusions: Four ferroptosis-associated potential hub genes (UTP6 (U3 small nucleolar RNA-associated protein 6), PRKACB (Protein kinase CAMP-Activated catalytic subunit beta), AATF (Anti-Apoptotic transcription factor), and NOC4L (Nucleolar complex associated 4 homolog)) were identified in the colonic mucosa. Our study could provide potential diagnostic candidate genes for UC.