AI Article Synopsis

  • - The study analyzed over 373,000 single-cell transcriptomes from colorectal cancer patients to better understand the diversity of epithelial cells, revealing distinct genetic and gene expression differences among malignant cells.
  • - Two new intrinsic subtypes, iCMS2 and iCMS3, were identified, with iCMS3 linked to worse outcomes and encompassing both microsatellite unstable (MSI-H) and some microsatellite-stable (MSS) cancers.
  • - The research proposes a refined 'IMF' classification that incorporates intrinsic epithelial subtype, microsatellite instability status, and fibrosis, leading to five distinct subtypes of colorectal cancer.

Article Abstract

The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined 'IMF' classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279158PMC
http://dx.doi.org/10.1038/s41588-022-01100-4DOI Listing

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