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High-Resolution Spatial Proteomics Characterises Colorectal Cancer Consensus Molecular Subtypes.

Batuhan Kisakol1, Anna Sturrock1, Sanghee Cho2

  • 1Department of Physiology and Medical Physics & RCSI Centre for Systems Medicine, RCSI University of Medicine and Health Sciences, 123 St Stephen's Green, Dublin 2, Ireland.

Biorxiv : the Preprint Server for Biology
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Summary
This summary is machine-generated.

This study reveals spatial protein atlases of colorectal cancer (CRC) subtypes, detailing cellular differences and tumor microenvironments at single-cell resolution to advance precision medicine.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Proteomics

Background:

  • Consensus molecular subtypes (CMS) offer insights into colorectal cancer (CRC) biology and heterogeneity.
  • Traditional bulk transcriptomics for CRC subtyping lacks spatial and single-cell resolution.

Purpose of the Study:

  • To investigate intratumoral heterogeneity within CMS subtypes of CRC.
  • To generate spatially resolved single-cell protein profiles for a comprehensive atlas of CRC.

Main Methods:

  • Tissue microarrays from 222 CRC patients were stained for 54 markers.
  • Spatially resolved single-cell protein profiling of over 2 million cells was performed.
  • Cancer, stromal, and immune cells were segmented for comparative analysis across CMS subtypes.

Main Results:

  • Tissue atlases revealed distinct cell types, spatial organization, and protein profiles for CMS 1-4.
  • CMS1 tumors showed increased immune cells and glycolysis; CMS2 exhibited immune segregation and proliferation.
  • CMS3 tumors had clustered cancer cells with high RIP3; CMS4 displayed stromal-centric, immune-evasive features.

Conclusions:

  • A spatial protein atlas of CRC at single-cell resolution was generated.
  • Novel aspects of CMS tumor structures and microenvironments were elucidated.