Identification of Common and Distinct Pathways in Inflammatory Bowel Disease and Colorectal Cancer: A Hypothesis Based on Weighted Gene Co-Expression Network Analysis

Afshin Derakhshani; Darya Javadrashid; Nima Hemmat; Antoine Dufour; Antonio Giovanni Solimando; Mahdi Abdoli Shadbad; Pascal H G Duijf; Oronzo Brunetti; Nicola Silvestris; Behzad Baradaran

doi:10.3389/fgene.2022.848646

Identification of Common and Distinct Pathways in Inflammatory Bowel Disease and Colorectal Cancer: A Hypothesis Based on Weighted Gene Co-Expression Network Analysis

Front Genet. 2022 Mar 31:13:848646. doi: 10.3389/fgene.2022.848646. eCollection 2022.

Authors

Afshin Derakhshani¹, Darya Javadrashid², Nima Hemmat², Antoine Dufour^{3

4}, Antonio Giovanni Solimando⁵, Mahdi Abdoli Shadbad⁶, Pascal H G Duijf^{7

8

9}, Oronzo Brunetti¹⁰, Nicola Silvestris¹¹, Behzad Baradaran^{2

12}

Affiliations

¹ Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, AB, Canada.
² Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
³ Departments of Physiology and Pharmacology, University of Calgary, Calgary, AB, Canada.
⁴ McCaig Insitute, Hotchkiss Brain Institute and Snyder Institute for Chronic Diseases, University of Calgary, Calgary, AB, Canada.
⁵ Department of Biomedical Sciences and Human Oncology, School of Medicine, Aldo Moro University of Bari, Bari, Italy.
⁶ Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran.
⁷ School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, Australia.
⁸ Centre for Data Science, Queensland University of Technology, Brisbane, QLD, Australia.
⁹ Translational Research Institute, University of Queensland Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia.
¹⁰ Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy.
¹¹ Medical Oncology Unit, Department of Human Pathology "G. Barresi" , University of Messina, Messina, Italy.
¹² Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.

Abstract

Patients with inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, are at higher risk to develop colorectal cancer (CRC). However, the underlying mechanisms of this predisposition remain elusive. We performed in-depth comparative computational analyses to gain new insights, including weighted gene co-expression network analysis (WGCNA) and gene ontology and pathway enrichment analyses, using gene expression datasets from IBD and CRC patients. When individually comparing IBD and CRC to normal control samples, we identified clusters of highly correlated genes, differentially expressed genes, and module-trait associations specific for each disease. When comparing IBD to CRC, we identified common hub genes and commonly enriched pathways. Most notably, IBD and CRC share significantly increased expression of five genes (MMP10, LCN2, REG1A, REG3A, and DUOX2), enriched inflammatory and neutrophil activation pathways and, most notably, highly significant enrichment of IL-4 and IL-13 signaling. Thus, our work expands our knowledge about the intricate relationship between IBD and CRC development and provides new rationales for developing novel therapeutic strategies.

Keywords: WGCNA; colorectal cancer; inflammatory bowel disease; pathogenesis; systems biology.