Construction of molecular subgroups of ulcerative colitis

Eur Rev Med Pharmacol Sci. 2023 Oct;27(19):9333-9345. doi: 10.26355/eurrev_202310_33961.

Abstract

Objective: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition.

Patients and methods: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups.

Results: Patients with UC were classified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-α antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients.

Conclusions: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC.

MeSH terms

  • Colitis, Ulcerative* / diagnosis
  • Colitis, Ulcerative* / drug therapy
  • Colitis, Ulcerative* / genetics
  • Gene Expression Profiling
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Mesalamine / therapeutic use
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Mesalamine
  • Tumor Necrosis Factor-alpha
  • PLEKHO1 protein, human
  • Intracellular Signaling Peptides and Proteins