A broad cuproptosis landscape in inflammatory bowel disease

• DOI: 10.3389/fimmu.2022.1031539
• Publication Date: 2022-11-03T08:33:29Z
• Authors: Yuan Chen; Xinfang Li; Ran Sun; Jiamin Ji; Fan Yang; Weiliang Tian; Wu Ji; Qian Huang
• Keywords: Gene signature

Background Cuproptosis, a genetic process of copper-dependent cell death linked to mitochondria respiration, demonstrates its correlation with inhibiting tumoral angiogenesis and motility. Recent studies have developed systematic bioinformatics frameworks identify the association cuproptosis tumors but any non-neoplastic diseases. Therefore, against background an increased incidence inflammatory bowel disease (IBD), landscape regulation in IBD is critical need be investigated. Methods The differentially expressed cuproptosis-related genes (DECRGs) were identified human sequencing profiles for four digestive disorders. Another independent datasets from GEO used as validation cohort. And experimental mice model provides another method. Using single sample gene set enrichment analysis (ssGSEA), receiver operating characteristic (ROC) curve, CIBERSORT, consensus clustering algorithms, we explored between immune score genes, well diagnostic value these genes. Molecular docking screened potential interaction drugs structural regulator by Autodock Vina. Results Cuproptosis-related regulators exhibited extensive differential expression Crohn’s Disease (CD), Ulcerative Colitis (UC), Celiac (CEL), IBD-induced cancer (IBD-CA) that share common (PDHA1, DBT, DLAT, LIAS). DECRGs was reverified validated cohort immunohistochemistry assay. Moreover, signaling pathways ontology mainly focused on mitochondrial respiratory function, which highly enriched Gene (GSEA). According ssGSEA ROC, when considering regulators, showed robust infiltration IBD, area under ROC (AUC) 0.743. In addition, two clusters based exhibit different phenotypes. molecular results, methotrexate gained highest binding affinity main chain key compared remaining ten drugs. Conclusion widely risk variants, cells, drug efficacy IBD. Regulation may deeply influence occurrence development patients