Identification of novel N7-methylguanine-related gene signatures associated with ulcerative colitis and the association with biological therapy

Inflamm Res. 2023 Dec;72(12):2169-2180. doi: 10.1007/s00011-023-01806-z. Epub 2023 Oct 27.

Abstract

Objective: Ulcerative colitis (UC) is an inflammatory disease characterized by recurrent episodes of chronic intestinal inflammation. It is closely associated with immune dysregulation in the intestines. However, the mechanisms underlying the role of immune-related N7-methylguanosine (m7G) internal modification in UC remain unclear.

Methods: We conducted a screening of differentially expressed genes (DEGs) associated with m7G and performed immune infiltration analysis. We then investigated the correlation between m7G-related DEGs and immune cells or pathways. To further explore the functional implications, we conducted functional enrichment analysis to identify gene modules that strongly correlated with hub gene expression. In addition, we constructed a miRNA regulatory network for the hub genes in UC. Furthermore, we examined the association between hub genes and disease remission in UC patients undergoing biologic therapy.

Results: We obtained 13 m7G-related DEGs and conducted an in-depth analysis of immune infiltration. Among them, we identified five hub genes (NUDT7, NUDT12, POLR2H, QKI, and PRKCB) that showed diagnostic potential for UC. Through WGCNA and KEGG analysis, we found that gene modules strongly correlated with m7G hub gene expression were enriched in inflammation-related pathways. Furthermore, Kaplan-Meier survival analysis revealed a significant association between changes in hub gene expression levels and disease remission in UC patients undergoing biologic therapy.

Conclusion: The findings of this study demonstrate that five m7G-related DEGs, including the m7G-modified recognition protein QKI, play a key role in the occurrence and progression of UC intestinal inflammation, which is closely related to intestinal immunity. These results provide valuable insights into the mechanisms of m7G modification in UC development and offer new perspectives for exploring novel therapeutic targets for UC.

Keywords: Biologics; GEO dataset; Immune; Inflammatory bowel disease; Ulcerative colitis.

MeSH terms

  • Biological Therapy
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / genetics
  • Humans
  • Inflammation / genetics
  • MicroRNAs*

Substances

  • 7-methylguanine
  • MicroRNAs