DataSheet1_Identification of Common and Distinct Pathways in Inflammatory Bowel Disease and Colorectal Cancer: A Hypothesis Based on Weighted Gene Co-Expression Network Analysis.docx

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.

炎症性肠病（inflammatory bowel disease, IBD）患者，涵盖溃疡性结肠炎（ulcerative colitis）与克罗恩病（Crohn’s disease）两类人群，罹患结直肠癌（colorectal cancer, CRC）的风险显著升高。然而，这一易感倾向的潜在分子机制仍未明确。本研究借助IBD与CRC患者的基因表达数据集，开展了深入的比较计算分析，包含加权基因共表达网络分析（weighted gene co-expression network analysis, WGCNA）、基因本体（gene ontology）富集分析及通路富集分析。
在分别将IBD、CRC与正常对照样本进行比对时，我们鉴定出了针对每种疾病的高相关性基因簇、差异表达基因（differentially expressed genes）以及疾病特异性模块-性状关联特征。在对比IBD与CRC的分析中，我们还识别出二者共有的核心基因（hub genes）与共同富集的通路。尤为值得关注的是，IBD与CRC中共存在5个基因（MMP10、LCN2、REG1A、REG3A及DUOX2）的表达水平显著上调，且二者均富集炎症与中性粒细胞活化通路，最显著的是IL-4与IL-13信号通路的高度显著富集。
综上，本研究深化了学界对IBD与CRC发生发展之间复杂关联的认知，并为开发新型治疗策略提供了全新的理论依据。