Identification of differentially expressed genes, associated functional terms pathways, and candidate diagnostic biomarkers in inflammatory bowel diseases by bioinformatics analysis

Abstract

Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic inflammatory disorders caused by genetic influences, the immune system and environmental factors. However, the underlying pathogenesis of IBDs and the pivotal molecular interactions remain to be fully elucidated. The aim of the present study was to identify genetic signatures in patients with IBDs and elucidate the potential molecular mechanisms underlying IBD subtypes. The gene expression profiles of the GSE75214 datasets were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in UC and CD patients compared with controls using the GEO2R tool. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of DEGs were performed using DAVID. Furthermore, protein-protein interaction (PPI) networks of the DEGs were constructed using Cytoscape software. Subsequently, significant modules were selected and the hub genes were identified. In the GO and KEGG pathway analysis, the top enriched pathways in UC and CD included Staphylococcus aureus infection, rheumatoid arthritis, complement and coagulation cascades, PI3K/Akt signaling pathway and osteoclast differentiation. In addition, the GO terms in the category biological process significantly enriched by these genes were inflammatory response, immune response, leukocyte migration, cell adhesion, response to molecules of bacterial origin and extracellular matrix (ECM) organization. However, several other biological processes (GO terms) and pathways (e.g., ‘chemotaxis’, ‘collagen catabolic process’ and ‘ECM-receptor interaction’) exhibited significant differences between the two subtypes of IBD. The top 10 hub genes were identified from the PPI network using respective DEGs. Of note, the hub genes G protein subunit gamma 11 (GNG11), G protein subunit beta 4 (GNB4), Angiotensinogen (AGT), Phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) and C-C motif chemokine receptor 7 (CCR7) are disease-specific and may be used as biomarkers for differentiating UC from CD. Furthermore, module analysis further confirmed that common significant pathways involved in the pathogenesis of IBD subtypes were associated with chemokine-induced inflammation, innate immunity, adapted immunity and infectious microbes. In conclusion, the present study identified DEGs, key target genes, functional pathways and enrichment analysis of IBDs, enhancing the understanding of the pathogenesis of IBDs and also advancing the clarification of the underlying molecular mechanisms of UC and CD. Furthermore, these results may provide potential molecular targets and diagnostic biomarkers for UC and CD.

Identification of Differential Intestinal Mucosa Transcriptomic Biomarkers for Ulcerative Colitis by Bioinformatics Analysis

“…Furthermore, the KEGG pathway analysis revealed that the common DEGs were particularly enriched in cytokine-cytokine receptor interaction, TNF signaling pathway, chemokine signaling pathway, pertussis, and rheumatoid arthritis. Multiple immune and inflammatory signaling pathways, including the cytokine-cytokine receptor interaction, TNF signaling pathway, and chemokine signaling pathway, are activated and involved in the process of intestinal inflammation [ 8 , 21 ]. Previous studies have demonstrated that the immune-inflammatory response pathway was closely associated with the pathogenesis of UC [ 22 , 23 ], which is mediated by a complex and dynamic relationship between immune cells and cytokines.…”

Possible role of microRNA miRNA-IL-25 interaction in mice with ulcerative colitis

“…A previous web-based database study that compared the differences in the gene expressions of UC and CD found that chemokine receptor 7 (CCR7) and IL-8 of the chemokine pathway occupy important sites in the regulation of UC network. This finding suggests an important role of the chemokine signaling pathway in UC [17]. Apoptosis frequently occurring in the epithelial cells and lymphocytes is a common cell biological event that contributes to disrupted barrier function and UC development [18][19][20][21][22].…”

Identification of drug targets and potential molecular mechanisms for Wantong Jingu Tablet extract in treatment of rheumatoid arthritis: bioinformatics analysis of fibroblast-like synoviocytes

“…Recent developments in bioinformatics and molecular biology have led to high-throughput sequencing (RNA-seq), which can simultaneously measure the expression of many genes [10,11]. Many researchers have used these techniques to characterize the mechanisms of various diseases and to identify potential therapeutic targets [12,13]. Therefore, we will apply the RNA-seq technology and corresponding bioinformatics analysis to identify the molecular mechanisms, biological processes, and potential drug targets in this study.…”