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Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer
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Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer
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Journal Article
Single-cell morphological and topological atlas reveals the ecosystem diversity of human breast cancer
2023
Overview
Digital pathology allows computerized analysis of tumor ecosystem using whole slide images (WSIs). Here, we present single-cell morphological and topological profiling (sc-MTOP) to characterize tumor ecosystem by extracting the features of nuclear morphology and intercellular spatial relationship for individual cells. We construct a single-cell atlas comprising 410 million cells from 637 breast cancer WSIs and dissect the phenotypic diversity within tumor, inflammatory and stroma cells respectively. Spatially-resolved analysis identifies recurrent micro-ecological modules representing locoregional multicellular structures and reveals four breast cancer ecotypes correlating with distinct molecular features and patient prognosis. Further analysis with multiomics data uncovers clinically relevant ecosystem features. High abundance of locally-aggregated inflammatory cells indicates immune-activated tumor microenvironment and favorable immunotherapy response in triple-negative breast cancers. Morphological intratumor heterogeneity of tumor nuclei correlates with cell cycle pathway activation and CDK inhibitors responsiveness in hormone receptor-positive cases. sc-MTOP enables using WSIs to characterize tumor ecosystems at the single-cell level.
Whole-slide images (WSI) and digital pathology are valuable approaches for the analysis of tumours and their microenvironments. Here, the authors present scMTOP, a framework to characterise tumour ecosystems and intercellular relationships at the single-cell level from WSIs, which they apply to breast cancer samples.
