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Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature

Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant pre...

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Autores principales: Tang, Yuhui, Tian, Wenwen, Xie, Jindong, Zou, Yutian, Wang, Zehao, Li, Ning, Zeng, Yan, Wu, Linyu, Zhang, Yue, Wu, Song, Xie, Xiaoming, Yang, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009264/
https://www.ncbi.nlm.nih.gov/pubmed/35432381
http://dx.doi.org/10.3389/fimmu.2022.843515
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author Tang, Yuhui
Tian, Wenwen
Xie, Jindong
Zou, Yutian
Wang, Zehao
Li, Ning
Zeng, Yan
Wu, Linyu
Zhang, Yue
Wu, Song
Xie, Xiaoming
Yang, Lu
author_facet Tang, Yuhui
Tian, Wenwen
Xie, Jindong
Zou, Yutian
Wang, Zehao
Li, Ning
Zeng, Yan
Wu, Linyu
Zhang, Yue
Wu, Song
Xie, Xiaoming
Yang, Lu
author_sort Tang, Yuhui
collection PubMed
description Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that tumor cells exhibit considerable plasticity based on fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of fatty acid metabolism in breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of tumor immune microenvironment, and the predictive significance in therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of fatty acid metabolism in breast cancer, supporting novel insights into breast cancer patients’ prognosis and administrating effective immunotherapy.
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spelling pubmed-90092642022-04-15 Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature Tang, Yuhui Tian, Wenwen Xie, Jindong Zou, Yutian Wang, Zehao Li, Ning Zeng, Yan Wu, Linyu Zhang, Yue Wu, Song Xie, Xiaoming Yang, Lu Front Immunol Immunology Fatty acid metabolism has been deciphered to augment tumorigenesis and disease progression in addition to therapy resistance via strengthened lipid synthesis, storage, and catabolism. Breast cancer is strongly associated with the biological function of fatty acid metabolism owing to the abundant presence of adipocytes in breast tissue. It has been unraveled that tumor cells exhibit considerable plasticity based on fatty acid metabolism, responding to extra-tumoral and a range of metabolic signals, in which tumor microenvironment plays a pivotal role. However, the prognostic significance of fatty acid metabolism in breast cancer remains to be further investigated. Alongside these insights, we retrieved 269 reliable fatty acid metabolism-related genes (FMGs) and identified the landscape of copy number variations and expression level among those genes. Additionally, 11 overall survival-related FMGs were clarified by univariate Cox hazards regression analysis in The Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases. Subsequently, a prognostic signature based on 6 overall survival (OS)-related FMGs was generated using Lasso Cox hazards regression analysis in TCGA dataset and was validated in two external cohorts. The correlation between the signature and several essential clinical parameters, including T, N, and PAM50 subtypes, was unveiled by comparing the accumulating signature value in various degrees. Furthermore, an optimal nomogram incorporating the signature, age, and American Joint Committee on Cancer (AJCC) stage was constructed, and the discrimination was verified by C-index, the calibration curve, and the decision curve analysis. The underlying implications for immune checkpoints inhibitors, the landscape of tumor immune microenvironment, and the predictive significance in therapy resistance to diverse strategies were depicted ultimately. In conclusion, our findings indicate the potential prognostic connotation of fatty acid metabolism in breast cancer, supporting novel insights into breast cancer patients’ prognosis and administrating effective immunotherapy. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9009264/ /pubmed/35432381 http://dx.doi.org/10.3389/fimmu.2022.843515 Text en Copyright © 2022 Tang, Tian, Xie, Zou, Wang, Li, Zeng, Wu, Zhang, Wu, Xie and Yang 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
Tang, Yuhui
Tian, Wenwen
Xie, Jindong
Zou, Yutian
Wang, Zehao
Li, Ning
Zeng, Yan
Wu, Linyu
Zhang, Yue
Wu, Song
Xie, Xiaoming
Yang, Lu
Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
title Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
title_full Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
title_fullStr Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
title_full_unstemmed Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
title_short Prognosis and Dissection of Immunosuppressive Microenvironment in Breast Cancer Based on Fatty Acid Metabolism-Related Signature
title_sort prognosis and dissection of immunosuppressive microenvironment in breast cancer based on fatty acid metabolism-related signature
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9009264/
https://www.ncbi.nlm.nih.gov/pubmed/35432381
http://dx.doi.org/10.3389/fimmu.2022.843515
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