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Metabolism and response to stress gene signatures reveal ulcerative colitis heterogeneity and identify patients with increased response to therapy

  • 0Alimentiv Inc., London, ON, Canada.
Journal of Crohn's & Colitis +

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June 9, 2025

|

June 9, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

We identified novel gene signatures to stratify ulcerative colitis (UC) patients into subtypes. This approach helps predict treatment response and identify patients less likely to benefit from therapies.

Area Of Science

  • Gastroenterology
  • Molecular Biology
  • Immunology

Background

  • Ulcerative colitis (UC) treatment outcomes vary significantly due to patient-specific factors like target variability and resistance mechanisms.
  • Current therapies show inconsistent remission and response rates in clinical trials.
  • Patient heterogeneity is a key challenge in UC treatment.

Purpose Of The Study

  • To stratify UC patients into subtypes by analyzing mucosal biopsy transcriptomics data.
  • To identify novel gene signatures for characterizing UC heterogeneity.
  • To predict treatment response based on identified patient subtypes.

Main Methods

  • Transcriptomics data from UC clinical trials (andecaliximab, ustekinumab, infliximab, adalimumab) were analyzed.
  • Eleven Reactome gene sets were scored for gene signature enrichment.
  • Metabolism and Response to Stress (MARS) signatures were developed and applied to classify patients.

Main Results

  • Five MARS gene sets correlated with non-disease mucosa, and six correlated with disease-related mucosa.
  • Clustering of andecaliximab trial data revealed three patient clusters based on MARS scores.
  • Patients with low non-disease/high disease-related MARS scores were less likely to respond to therapy across different UC drug trials.

Conclusions

  • A novel, multi-dimensional gene signature (MARS) was identified to characterize UC patient heterogeneity.
  • This signature can identify UC patients with a lower likelihood of responding to therapy.
  • The MARS signature approach can refine clinical trial populations and aid in developing targeted therapies for difficult-to-treat UC patients.

Keywords:

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