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

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.

CTLA-4 silencing in dendritic cells loaded with colorectal cancer cell lysate improves autologous T cell responses in vitro

“…Colorectal cancer (CRC) is the third most frequent cancer globally, accounting for approximately 935,000 deaths per year, and has been ranked as the second major cause of cancer deaths in 2020 ( 16 ). Chemotherapy, surgery, and radiotherapy are among the conventional treatments for this malignancy ( 17 , 18 ). These conventional therapies may be related to adverse side effects, i.e., chemotherapy resistance, systemic toxicity, and cancer recurrence ( 2 , 19 ).…”

A scoping review on the significance of programmed death-ligand 1-inhibiting microRNAs in non-small cell lung treatment: A single-cell RNA sequencing-based study

“…System biology approaches have provided valuable insights into the expression profile of various human conditions ( 61 , 62 ). Following systematically reviewing the literature, we aimed to leverage the data obtained from system biology to predict the potential circRNA/PD-L1-targeting miRs in NSCLC tissues.…”

Hierarchical cell-type identifier accurately distinguishes immune-cell subtypes enabling precise profiling of tissue microenvironment with single-cell RNA-sequencing

“…M1 macrophages produce pro-inflammatory cytokines such as IL-6, IL-1β, and TNF-α, whereas the M2a, M2b, and M2c subtypes are associated with the responses to anti-inflammatory activity (54,55). However, an aberrant polarization of macrophages such as abundant M1 and depleted M2 could be observed in the progression of UC(56) and M1-skewed transcriptional program in macrophages were known to ignite chronic activation of NLRP3 inflammasome causing inflammatory bowel disease (IBD), such as ulcerative colitis(UC) (57)(58)(59). Although M2 macrophages are associated with anti-inflammatory activities in general, M2b is known to secret pro-inflammatory cytokines as well, including IL-6, IL-1β, and TNF-α, acting both pro-and anti-inflammatory reaction, and play an important role in the IBD (60).…”