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Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer
BACKGROUND: Prior studies have highlighted that novel programmed cell death (PCD) modalities, including ferroptosis, pyroptosis, and necroptosis, are correlated with tumor progression and antitumor immunity. Nonetheless, comprehensive analysis of tumor microenvironment (TME) profiles mediated by the...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403178/ https://www.ncbi.nlm.nih.gov/pubmed/36032140 http://dx.doi.org/10.3389/fimmu.2022.942765 |
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author | Xu, Lijun |
author_facet | Xu, Lijun |
author_sort | Xu, Lijun |
collection | PubMed |
description | BACKGROUND: Prior studies have highlighted that novel programmed cell death (PCD) modalities, including ferroptosis, pyroptosis, and necroptosis, are correlated with tumor progression and antitumor immunity. Nonetheless, comprehensive analysis of tumor microenvironment (TME) profiles mediated by the crosstalk of distinct PCD forms has not been conducted in breast cancer (BC). METHODS: Here, we curated 34 identified PCD-associated genes (PCDAGs) and applied the consensus clustering algorithm to establish PCD-mediated tumor patterns in BC. Subsequently, based on prognostic differentially expressed genes extracted from distinct PCD-mediated patterns, we applied the LASSO algorithm to construct CD_Score. Furthermore, the correlation analysis between CD_Score and TME features, molecular subtypes, clinicopathological characteristics, drug response, and immunotherapeutic efficacy was performed. RESULTS: Three distinct PCD-clusters were determined among 2,038 BC samples, which did not only display different clinical outcomes but highly correlated to the established immunological tumor phenotypes: “desert,” “excluded,” and “inflamed” immune profiles. Based on the CD_Score derived from the PCD-related gene signature, BC patients could be stratified into CD_Score-low and -high group, of which the former displayed satisfactory survival outcome and enhanced immune infiltration. Further exploration identified that the CD_Score-high group significantly correlated with elevated neoantigen load and higher mutation frequency in SMGs (e.g., TP53 and MAP3K1) and reduced expression of immune checkpoint proteins. CONCLUSIONS: This research is the first to emphasize the close relationship between distinct cell death modalities and the diversity and complexity of immune infiltration in TME. We established the CD_Score, which could help enhance our cognition of TME features and facilitate the clinical application of immunotherapy. |
format | Online Article Text |
id | pubmed-9403178 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94031782022-08-26 Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer Xu, Lijun Front Immunol Immunology BACKGROUND: Prior studies have highlighted that novel programmed cell death (PCD) modalities, including ferroptosis, pyroptosis, and necroptosis, are correlated with tumor progression and antitumor immunity. Nonetheless, comprehensive analysis of tumor microenvironment (TME) profiles mediated by the crosstalk of distinct PCD forms has not been conducted in breast cancer (BC). METHODS: Here, we curated 34 identified PCD-associated genes (PCDAGs) and applied the consensus clustering algorithm to establish PCD-mediated tumor patterns in BC. Subsequently, based on prognostic differentially expressed genes extracted from distinct PCD-mediated patterns, we applied the LASSO algorithm to construct CD_Score. Furthermore, the correlation analysis between CD_Score and TME features, molecular subtypes, clinicopathological characteristics, drug response, and immunotherapeutic efficacy was performed. RESULTS: Three distinct PCD-clusters were determined among 2,038 BC samples, which did not only display different clinical outcomes but highly correlated to the established immunological tumor phenotypes: “desert,” “excluded,” and “inflamed” immune profiles. Based on the CD_Score derived from the PCD-related gene signature, BC patients could be stratified into CD_Score-low and -high group, of which the former displayed satisfactory survival outcome and enhanced immune infiltration. Further exploration identified that the CD_Score-high group significantly correlated with elevated neoantigen load and higher mutation frequency in SMGs (e.g., TP53 and MAP3K1) and reduced expression of immune checkpoint proteins. CONCLUSIONS: This research is the first to emphasize the close relationship between distinct cell death modalities and the diversity and complexity of immune infiltration in TME. We established the CD_Score, which could help enhance our cognition of TME features and facilitate the clinical application of immunotherapy. Frontiers Media S.A. 2022-08-11 /pmc/articles/PMC9403178/ /pubmed/36032140 http://dx.doi.org/10.3389/fimmu.2022.942765 Text en Copyright © 2022 Xu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Xu, Lijun Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
title | Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
title_full | Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
title_fullStr | Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
title_full_unstemmed | Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
title_short | Crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
title_sort | crosstalk of three novel types of programmed cell death defines distinct microenvironment characterization and pharmacogenomic landscape in breast cancer |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403178/ https://www.ncbi.nlm.nih.gov/pubmed/36032140 http://dx.doi.org/10.3389/fimmu.2022.942765 |
work_keys_str_mv | AT xulijun crosstalkofthreenoveltypesofprogrammedcelldeathdefinesdistinctmicroenvironmentcharacterizationandpharmacogenomiclandscapeinbreastcancer |