Department of Anatomy, Biochemistry, and Physiology, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI, United States of America.
Department of Animal Science and Aquaculture, Dalhousie University, Truro, Nova Scotia, Canada.
PLoS One. 2022 Apr 22;17(4):e0267358. doi: 10.1371/journal.pone.0267358. eCollection 2022.
It has been indicated that there is an association between inflammatory bowel disease (IBD) and hepatocellular carcinoma (HCC). However, the molecular mechanism underlying the risk of developing HCC among patients with IBD is not well understood. The current study aimed to identify shared genes and potential pathways and regulators between IBD and HCC using a system biology approach. By performing the different gene expression analyses, we identified 871 common differentially expressed genes (DEGs) between IBD and HCC. Of these, 112 genes overlapped with immune genes were subjected to subsequent bioinformatics analyses. The results revealed four hub genes (CXCL2, MMP9, SPP1 and SRC) and several other key regulators including six transcription factors (FOXC1, FOXL1, GATA2, YY1, ZNF354C and TP53) and five microRNAs (miR-124-3p, miR-34a-5p, miR-1-3p, miR-7-5p and miR-99b-5p) for these disease networks. Protein-drug interaction analysis discovered the interaction of the hub genes with 46 SRC-related and 11 MMP9- related drugs that may have a therapeutic effect on IBD and HCC. In conclusion, this study sheds light on the potential connecting mechanisms of HCC and IBD.
已经表明，炎症性肠病（IBD）和肝细胞癌（HCC）之间存在关联。然而，IBD 患者发生 HCC 的风险的潜在分子机制尚不清楚。本研究旨在采用系统生物学方法，确定 IBD 和 HCC 之间的共享基因和潜在途径及调控因子。通过进行不同的基因表达分析，我们在 IBD 和 HCC 之间鉴定出 871 个共同差异表达基因（DEG）。其中，与免疫基因重叠的 112 个基因被进一步进行了生物信息学分析。结果揭示了四个枢纽基因（CXCL2、MMP9、SPP1 和 SRC）和其他几个关键调控因子，包括六个转录因子（FOXC1、FOXL1、GATA2、YY1、ZNF354C 和 TP53）和五个 microRNAs（miR-124-3p、miR-34a-5p、miR-1-3p、miR-7-5p 和 miR-99b-5p），这些基因和调控因子参与了这些疾病网络。蛋白-药物相互作用分析发现，枢纽基因与 46 个 SRC 相关药物和 11 个 MMP9 相关药物相互作用，这些药物可能对 IBD 和 HCC 具有治疗作用。总之，本研究揭示了 HCC 和 IBD 之间潜在的关联机制。
