ArticlebioRxiv : the preprint server for biology2025
High-Resolution Spatial Proteomics Characterises Colorectal Cancer Consensus Molecular Subtypes.
Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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17 authors.
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Abstract
Background: Identification of the consensus molecular subtypes (CMS) opened significant potential for understanding the tumor biology and intertumoral heterogeneity of colorectal cancer (CRC). However, molecular subtyping in CRC traditionally relies on bulk transcriptomics, therefore, lacks spatial and single-cell level aspect. Methods: We constructed tissue microarrays using tumor cores from 222 CRC patients. Arrays were stained and imaged using 54 cell identity and cancer hallmark markers, delivering spatially resolved protein profiles of >2 million cells. RNA sequencing data and CMS classification were also available for these patients. After segmentation of cancer, stromal and immune cells, we investigated intratumoral heterogeneity within CMS subtypes using spatially resolved single-cell protein profiling (>2 million cells). We compared cell types, their spatial organization and their expression of cancer hallmark-related proteins in CMS 1-4 subtypes. Results: We revealed tissue atlases illustrating the cell types/states, spatial heterogeneity, cellular neighborhoods, cellular network, and single-cell protein profiles of CMS tumors. CMS1 tumors had more CD3 Conclusion: We present a spatial protein atlas of CRC at single-cell resolution and demonstrate novel aspects of CMS tumour structures.
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