Single‐cell protein profiling defines cell populations associated with triple‐negative breast cancer aggressiveness

Triple‐negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single‐cell techniques in combination with next‐...

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Vydáno v:Molecular oncology Ročník 17; číslo 6; s. 1024 - 1040
Hlavní autoři: Kvokačková, Barbora, Fedr, Radek, Kužílková, Daniela, Stuchlý, Jan, Vávrová, Adéla, Navrátil, Jiří, Fabian, Pavel, Ondruššek, Róbert, Ovesná, Petra, Remšík, Ján, Bouchal, Jan, Kalina, Tomáš, Souček, Karel
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States John Wiley & Sons, Inc 01.06.2023
John Wiley and Sons Inc
Wiley
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ISSN:1574-7891, 1878-0261, 1878-0261
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Abstract Triple‐negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single‐cell techniques in combination with next‐generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single‐cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial‐mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor‐associated stroma. Furthermore, in a retrospective tissue‐microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential. The extensive heterogeneity of triple‐negative breast cancer (TNBC) affects disease progression and therapeutic response. To investigate TNBC heterogeneity in more detail, we profiled 26 treatment‐naïve primary TNBC at the single‐cell level using mass cytometry. We introduced a new clinically relevant Ki‐67+LNR index and identified distinct tumor and stromal populations associated with clinical observations.
AbstractList Triple‐negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single‐cell techniques in combination with next‐generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single‐cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial‐mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor‐associated stroma. Furthermore, in a retrospective tissue‐microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential. The extensive heterogeneity of triple‐negative breast cancer (TNBC) affects disease progression and therapeutic response. To investigate TNBC heterogeneity in more detail, we profiled 26 treatment‐naïve primary TNBC at the single‐cell level using mass cytometry. We introduced a new clinically relevant Ki‐67+LNR index and identified distinct tumor and stromal populations associated with clinical observations.
Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.
Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.
Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single-cell techniques in combination with next-generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single-cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial-mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor-associated stroma. Furthermore, in a retrospective tissue-microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential.
Triple‐negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic, extensive intratumoral heterogeneity that promotes disease progression and influences drug response. Single‐cell techniques in combination with next‐generation computation provide an unprecedented opportunity to identify molecular events with therapeutic potential. Here, we describe the generation of a comprehensive mass cytometry panel for multiparametric detection of 23 phenotypic markers and 13 signaling molecules. This single‐cell proteomic approach allowed us to explore the landscape of TNBC heterogeneity, with particular emphasis on the tumor microenvironment. We prospectively profiled freshly resected tumors from 26 TNBC patients. These tumors contained phenotypically distinct subpopulations of cancer and stromal cells that were associated with the patient's clinical status at the time of surgery. We further classified the epithelial‐mesenchymal plasticity of tumor cells, and molecularly defined phenotypically diverse populations of tumor‐associated stroma. Furthermore, in a retrospective tissue‐microarray TNBC cohort, we showed that the level of CD97 at the time of surgery has prognostic potential. The extensive heterogeneity of triple‐negative breast cancer (TNBC) affects disease progression and therapeutic response. To investigate TNBC heterogeneity in more detail, we profiled 26 treatment‐naïve primary TNBC at the single‐cell level using mass cytometry. We introduced a new clinically relevant Ki‐67+LNR index and identified distinct tumor and stromal populations associated with clinical observations.
Author Ondruššek, Róbert
Fabian, Pavel
Remšík, Ján
Stuchlý, Jan
Kvokačková, Barbora
Ovesná, Petra
Bouchal, Jan
Kalina, Tomáš
Navrátil, Jiří
Vávrová, Adéla
Fedr, Radek
Souček, Karel
Kužílková, Daniela
AuthorAffiliation 2 International Clinical Research Center St. Anne's University Hospital Brno Czech Republic
7 Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic
9 Department of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry Palacký University and University Hospital Olomouc Czech Republic
11 Institute of Biostatistics and Analyses, Faculty of Medicine Masaryk University Brno Czech Republic
3 Department of Experimental Biology, Faculty of Science Masaryk University Brno Czech Republic
4 Childhood Leukaemia Investigation Prague Czech Republic
12 Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York City NY USA
6 Faculty of Science Charles University Prague Czech Republic
5 Department of Pediatric Haematology and Oncology, 2nd Faculty of Medicine Charles University Prague and University Hospital Motol Czech Republic
8 Department of Oncological Pathology Masaryk Memor
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2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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Issue 6
Keywords unsupervised machine learning algorithm
triple-negative breast cancer
phenotypic plasticity
mass cytometry
single-cell profiles
tumor heterogeneity
Language English
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Snippet Triple‐negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic,...
Triple-negative breast cancer (TNBC) is an aggressive and complex subtype of breast cancer that lacks targeted therapy. TNBC manifests characteristic,...
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StartPage 1024
SubjectTerms Antibodies
Bar codes
Breast Cancer
Cells
Cloning
Cytometry
Fibroblasts
Glycerol
mass cytometry
Metastasis
Patients
phenotypic plasticity
Proteins
Proteomics
Single-cell protein
single‐cell profiles
Stromal cells
Surgery
triple‐negative breast cancer
Tumor cells
tumor heterogeneity
Tumor microenvironment
Tumors
unsupervised machine learning algorithm
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Title Single‐cell protein profiling defines cell populations associated with triple‐negative breast cancer aggressiveness
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Volume 17
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