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Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications
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Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications
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Journal Article
Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications
2024
Overview
While triple-negative breast cancer (TNBC) is known to be heterogeneous at the genomic and transcriptomic levels, spatial information on tumor organization and cell composition is still lacking. Here, we investigate TNBC tumor architecture including its microenvironment using spatial transcriptomics on a series of 92 patients. We perform an in-depth characterization of tumor and stroma organization and composition using an integrative approach combining histomorphological and spatial transcriptomics. Furthermore, a detailed molecular characterization of tertiary lymphoid structures leads to identify a gene signature strongly associated to disease outcome and response to immunotherapy in several tumor types beyond TNBC. A stepwise clustering analysis identifies nine TNBC spatial archetypes, further validated in external datasets. Several spatial archetypes are associated with disease outcome and characterized by potentially actionable features. In this work, we provide a comprehensive insight into the complexity of TNBC ecosystem with potential clinical relevance, opening avenues for treatment tailoring including immunotherapy.
Triple-negative breast cancer (TNBC) is a heterogenous disease with several molecular subtypes previously described. Here the authors perform a spatial transcriptomics analysis on a series of 92 patients, providing additional insights into the heterogeneity of TNBC, with implications for clinical outcomes and therapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Research,Nature Portfolio
Subject
/ 38
/ 38/39
/ 38/91
/ Adult
/ Aged
/ Biochemistry, Genetics and Molecular Biology (all)
/ Biomarkers, Tumor - genetics
/ Biomarkers, Tumor - metabolism
/ Female
/ Gene Expression Profiling - methods
/ Gene Expression Regulation, Neoplastic
/ Humanities and Social Sciences
/ Humans
/ Oncology
/ Patients
/ Science
/ Sciences de la santé humaine
/ Stroma
/ Tertiary Lymphoid Structures
/ Tertiary Lymphoid Structures - genetics
/ Tertiary Lymphoid Structures - immunology
/ Tertiary Lymphoid Structures - pathology
/ Triple Negative Breast Neoplasms
/ Triple Negative Breast Neoplasms - genetics
/ Triple Negative Breast Neoplasms - pathology
/ Triple Negative Breast Neoplasms - therapy
/ Tumor Microenvironment - genetics
/ Tumor Microenvironment - immunology
/ Tumors
