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The consensus molecular subtypes of colorectal cancer

One-paragraph summary

An international consortium reconciled six independent expression-classification systems using 4,151 samples and defined four consensus molecular subtypes: CMS1 immune/MSI, CMS2 canonical, CMS3 metabolic and CMS4 mesenchymal, plus mixed/indeterminate tumors. CMS4 carried the worst relapse-free and overall survival, while CMS1 had poor survival after relapse (PMID 26457759).

Key findings

  • Four reproducible bulk-expression classes integrated previously discordant taxonomies.
  • CMS classes linked gene expression to genomic, epigenomic and clinical features.
  • CMS4 emphasized stromal/mesenchymal biology and adverse outcome.
  • Mixed classification made intratumor heterogeneity visible rather than forcing every sample into a class.

Limitations

  • Bulk RNA mixes malignant, immune and stromal cells.
  • Retrospective datasets and platform differences remained.
  • Prognostic separation did not prove treatment-predictive utility.
  • Primary/metastatic and pre/post-treatment stability was not established.

Why it matters

CMS became the common research language for colorectal expression biology, enabling cross-study comparison while also motivating single-cell efforts to separate epithelial-intrinsic from microenvironmental signals.

Cited by wiki pages

  • Overview
  • Molecular subtypes and tumor microenvironment
  • Biomarkers and liquid biopsy