A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape
Abstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-rela...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-09-01
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| Series: | Journal of Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12967-021-03076-x |
| _version_ | 1818661881250840576 |
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| author | Peiling Xie Rui An Shibo Yu Jianjun He Huimin Zhang |
| author_facet | Peiling Xie Rui An Shibo Yu Jianjun He Huimin Zhang |
| author_sort | Peiling Xie |
| collection | DOAJ |
| description | Abstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. Results Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. Conclusion Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations. |
| first_indexed | 2024-12-17T04:52:06Z |
| format | Article |
| id | doaj.art-9211a8986c4e4d4abca68ac68b1ef2de |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-17T04:52:06Z |
| publishDate | 2021-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-9211a8986c4e4d4abca68ac68b1ef2de2022-12-21T22:02:52ZengBMCJournal of Translational Medicine1479-58762021-09-0119111410.1186/s12967-021-03076-xA novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscapePeiling Xie0Rui An1Shibo Yu2Jianjun He3Huimin Zhang4Department of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Hepatological Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Breast Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract Background The diversity and plasticity behind ER+/PR−/HER2− breast cancer have not been widely explored. It is essential to identify heterogeneous microenvironment phenotypes and investigate specific genomic events driving the formation of these phenotypes. Methods Based on the immune-related gene expression profiles of 411 ER+/PR−/HER2− breast cancers in the METABRIC cohort, we used consensus clustering to identify heterogeneous immune subtypes and assessed their reproducibility in an independent meta-cohort including 135 patients collected from GEO database. We further analyzed the differences of cellular and molecular characteristics, and potential immune escape mechanism among immune subtypes. In addition, we constructed a transcriptional trajectory to visualize the distribution of individual patient. Results Our analysis identified and validated five reproducible immune subtypes with distinct cellular and molecular characteristics, potential immune escape mechanisms, genomic drivers, as well as clinical outcomes. An immune-cold subtype, with the least amount of lymphocyte infiltration, had a poorer prognosis. By contrast, an immune-hot subtype, which demonstrated the highest infiltration of CD8+ T cells, DCs and NK cells, and elevated IFN-γ response, had a comparatively favorable prognosis. Other subtypes showed more diverse gene expression and immune infiltration patterns with distinct clinical outcomes. Finally, our analysis revealed a complex immune landscape consisting of both discrete cluster and continuous spectrum. Conclusion Overall, this study revealed five heterogeneous immune subtypes among ER+/PR–/HER2− breast cancer, also provided important implications for clinical translations.https://doi.org/10.1186/s12967-021-03076-xBreast cancerER+/PR−/HER2−Immune classificationMulti-omics |
| spellingShingle | Peiling Xie Rui An Shibo Yu Jianjun He Huimin Zhang A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape Journal of Translational Medicine Breast cancer ER+/PR−/HER2− Immune classification Multi-omics |
| title | A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape |
| title_full | A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape |
| title_fullStr | A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape |
| title_full_unstemmed | A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape |
| title_short | A novel immune subtype classification of ER-positive, PR-negative and HER2-negative breast cancer based on the genomic and transcriptomic landscape |
| title_sort | novel immune subtype classification of er positive pr negative and her2 negative breast cancer based on the genomic and transcriptomic landscape |
| topic | Breast cancer ER+/PR−/HER2− Immune classification Multi-omics |
| url | https://doi.org/10.1186/s12967-021-03076-x |
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