Analysis of neutrophil extracellular trap‐related genes in Crohn's disease based on bioinformatics

• Published in: Journal of cellular and molecular medicine Vol. 28; no. 16; pp. e70013 - n/a
• Main Authors: Chen, Libin, Ai, Feiyan, Wu, Xing, Yu, Wentao, Jin, Xintong, Ma, Jian, Xiang, Bo, Shen, Shourong, Li, Xiayu
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2024; John Wiley and Sons Inc
• Subjects: Bioinformatics; biomarker; Biomarkers; Biopsy; CD4 antigen; Chemokines; Colon; Computational Biology - methods; Crohn Disease - genetics; Crohn Disease - immunology; Crohn Disease - pathology; Crohn's disease; Cytokines; Databases, Genetic; Datasets; Extracellular Traps - genetics; Extracellular Traps - metabolism; Gastrointestinal tract; Gene expression; Gene Expression Omnibus; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks; Genomes; Humans; immune infiltration; Inflammatory bowel diseases; Interferon regulatory factor 1; Leukocytes (neutrophilic); Macrophages; Microbicides; neutrophil extracellular traps; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Original; Pathogens; Phenotypes; Protein Interaction Maps - genetics; Proteins; Rheumatoid arthritis; Software; Statistical models; Systemic lupus erythematosus; Therapeutic applications; Tissue inhibitor of metalloproteinase 1; Crohn's disease; neutrophil extracellular traps; immune infiltration; biomarker; Gene Expression Omnibus; bioinformatics
• DOI: 10.1111/jcmm.70013
• ISSN: 1582-1838; 1582-4934

Crohn's disease (CD) presents with diverse clinical phenotypes due to persistent inflammation of the gastrointestinal tract. Its global incidence is on the rise. Neutrophil extracellular traps (NETs) are networks released by neutrophils that capture microbicidal proteins and oxidases targeting pathogens. Research has shown that NETs are implicated in the pathogenesis of several immune‐mediated diseases such as rheumatoid arthritis, systemic lupus erythematosus and inflammatory bowel disease. The goal of this study was to identify a panel of NET‐related genes to construct a diagnostic and therapeutic model for CD. Through analysis of the GEO database, we identified 1950 differentially expressed genes (DEGs) associated with CD. Gene enrichment and immune cell infiltration analyses indicate that neutrophil infiltrates and chemokine‐related pathways are predominantly involved in CD, with other immune cells such as CD4 and M1 macrophages also playing a role in disease progression. Utilizing weighted gene co‐expression network analysis (WGCNA) and protein–protein interaction (PPI) networks, we identified six hub genes (SPP1, SOCS3, TIMP1, IRF1, CXCL2 and CD274). To validate the accuracy of our model, we performed external validation with statistical differences(p < 0.05). Additionally, immunohistochemical experiments demonstrated higher protein expression of the hub genes in colonic tissues from CD patients compared to healthy subjects (p < 0.05). In summary, we identified six effective hub genes associated with NETs as potential diagnostic markers for CD. These markers not only offer targets for future research but also hold promise for the development of novel therapeutic interventions for CD.