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 |
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| Hlavní autoři: | , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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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. |
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| 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 |
| AuthorAffiliation_xml | – name: 2 International Clinical Research Center St. Anne's University Hospital Brno Czech Republic – name: 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 – name: 8 Department of Oncological Pathology Masaryk Memorial Cancer Institute Brno Czech Republic – name: 11 Institute of Biostatistics and Analyses, Faculty of Medicine Masaryk University Brno Czech Republic – name: 1 Department of Cytokinetics Institute of Biophysics of the Czech Academy of Sciences Brno Czech Republic – name: 6 Faculty of Science Charles University Prague Czech Republic – name: 4 Childhood Leukaemia Investigation Prague Czech Republic – name: 5 Department of Pediatric Haematology and Oncology, 2nd Faculty of Medicine Charles University Prague and University Hospital Motol Czech Republic – name: 7 Department of Comprehensive Cancer Care Masaryk Memorial Cancer Institute Brno Czech Republic – name: 10 Department of Pathology EUC Laboratoře CGB a.s. Ostrava Czech Republic – name: 3 Department of Experimental Biology, Faculty of Science Masaryk University Brno Czech Republic – name: 12 Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer Center New York City NY USA |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36550781$$D View this record in MEDLINE/PubMed |
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| Copyright | 2022 The Authors. published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. 2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. |
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| Keywords | unsupervised machine learning algorithm triple-negative breast cancer phenotypic plasticity mass cytometry single-cell profiles tumor heterogeneity |
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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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| 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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