Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications
Abstract 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 transc...
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Nature Portfolio
2024-11-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-54145-w |
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| author | Xiaoxiao Wang David Venet Frédéric Lifrange Denis Larsimont Mattia Rediti Linnea Stenbeck Floriane Dupont Ghizlane Rouas Andrea Joaquin Garcia Ligia Craciun Laurence Buisseret Michail Ignatiadis Marcela Carausu Nayanika Bhalla Yuvarani Masarapu Eva Gracia Villacampa Lovisa Franzén Sami Saarenpää Linda Kvastad Kim Thrane Joakim Lundeberg Françoise Rothé Christos Sotiriou |
| author_facet | Xiaoxiao Wang David Venet Frédéric Lifrange Denis Larsimont Mattia Rediti Linnea Stenbeck Floriane Dupont Ghizlane Rouas Andrea Joaquin Garcia Ligia Craciun Laurence Buisseret Michail Ignatiadis Marcela Carausu Nayanika Bhalla Yuvarani Masarapu Eva Gracia Villacampa Lovisa Franzén Sami Saarenpää Linda Kvastad Kim Thrane Joakim Lundeberg Françoise Rothé Christos Sotiriou |
| author_sort | Xiaoxiao Wang |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-ccc6eec04dde4ff3a3fd0330c0c3eaf5 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ccc6eec04dde4ff3a3fd0330c0c3eaf52024-12-01T12:36:08ZengNature PortfolioNature Communications2041-17232024-11-0115112210.1038/s41467-024-54145-wSpatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implicationsXiaoxiao Wang0David Venet1Frédéric Lifrange2Denis Larsimont3Mattia Rediti4Linnea Stenbeck5Floriane Dupont6Ghizlane Rouas7Andrea Joaquin Garcia8Ligia Craciun9Laurence Buisseret10Michail Ignatiadis11Marcela Carausu12Nayanika Bhalla13Yuvarani Masarapu14Eva Gracia Villacampa15Lovisa Franzén16Sami Saarenpää17Linda Kvastad18Kim Thrane19Joakim Lundeberg20Françoise Rothé21Christos Sotiriou22Breast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesDepartment of Pathology, University Hospital Center of LiègeDepartment of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesDepartment of Gene Technology, KTH Royal Institute of TechnologyBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesDepartment of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyDepartment of Gene Technology, KTH Royal Institute of TechnologyBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesBreast Cancer Translational Research Laboratory J-C Heuson, Institut Jules Bordet, Université Libre de Bruxelles, Hôpital Universitaire de BruxellesAbstract 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.https://doi.org/10.1038/s41467-024-54145-w |
| spellingShingle | Xiaoxiao Wang David Venet Frédéric Lifrange Denis Larsimont Mattia Rediti Linnea Stenbeck Floriane Dupont Ghizlane Rouas Andrea Joaquin Garcia Ligia Craciun Laurence Buisseret Michail Ignatiadis Marcela Carausu Nayanika Bhalla Yuvarani Masarapu Eva Gracia Villacampa Lovisa Franzén Sami Saarenpää Linda Kvastad Kim Thrane Joakim Lundeberg Françoise Rothé Christos Sotiriou Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications Nature Communications |
| title | Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications |
| title_full | Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications |
| title_fullStr | Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications |
| title_full_unstemmed | Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications |
| title_short | Spatial transcriptomics reveals substantial heterogeneity in triple-negative breast cancer with potential clinical implications |
| title_sort | spatial transcriptomics reveals substantial heterogeneity in triple negative breast cancer with potential clinical implications |
| url | https://doi.org/10.1038/s41467-024-54145-w |
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