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Integrating Bioinformatics and Experimental Validation Identifies SCD as a Ferroptosis-Related Immune Regulator and
Jingtong Wu1,2,3, Lixiang Zhou1, Dongmei Qiu1
1Department of Gastroenterology, Clinical Research Center for Gut Microbiota and Digestive Diseases of Fujian Province, The National Key Clinical Specialty, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361004, China.
Abstract:
This study investigates the role of ferroptosis-related genes (FRGs) in the intestinal inflammation of Crohn's disease (CD). Through integrated bioinformatics and experimental validation, we identified differentially expressed genes from RNA-seq data and intersected them with known FRGs to obtain ferroptosis-related differentially expressed genes (FEDGs). Functional enrichment and immune infiltration analyses were performed, and seven hub FEDGs were selected using machine learning. A diagnostic model based on these genes showed strong predictive ability. Immune analysis revealed significant associations with macrophages, neutrophils, dendritic cells, and CD4+ T cells. Protein expression of key hub genes was validated in clinical CD samples and a DSS-induced colitis model. Importantly, localized inhibition of SCD alleviated disease severity in experimental colitis. These findings highlight the involvement of ferroptosis in CD immune dysregulation and propose SCD as a potential therapeutic target.
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