Open Access

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

  • Authors:
    • Chunwei Cheng
    • Juan Hua
    • Jun Tan
    • Wei Qian
    • Lei Zhang
    • Xiaohua Hou
  • View Affiliations

  • Published online on: May 3, 2019     https://doi.org/10.3892/etm.2019.7541
  • Pages: 278-288
  • Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.
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July-2019
Volume 18 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Cheng C, Hua J, Tan J, Qian W, Zhang L and Hou X: Identification of differentially expressed genes, associated functional terms pathways, and candidate diagnostic biomarkers in inflammatory bowel diseases by bioinformatics analysis. Exp Ther Med 18: 278-288, 2019
APA
Cheng, C., Hua, J., Tan, J., Qian, W., Zhang, L., & Hou, X. (2019). Identification of differentially expressed genes, associated functional terms pathways, and candidate diagnostic biomarkers in inflammatory bowel diseases by bioinformatics analysis. Experimental and Therapeutic Medicine, 18, 278-288. https://doi.org/10.3892/etm.2019.7541
MLA
Cheng, C., Hua, J., Tan, J., Qian, W., Zhang, L., Hou, X."Identification of differentially expressed genes, associated functional terms pathways, and candidate diagnostic biomarkers in inflammatory bowel diseases by bioinformatics analysis". Experimental and Therapeutic Medicine 18.1 (2019): 278-288.
Chicago
Cheng, C., Hua, J., Tan, J., Qian, W., Zhang, L., Hou, X."Identification of differentially expressed genes, associated functional terms pathways, and candidate diagnostic biomarkers in inflammatory bowel diseases by bioinformatics analysis". Experimental and Therapeutic Medicine 18, no. 1 (2019): 278-288. https://doi.org/10.3892/etm.2019.7541