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Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer

BACKGROUND: Ferroptosis is a kind of programmed cell death that is characterized by iron dependence. It differs from apoptosis, necrosis, autophagy, pyroptosis, and other types of cell death. Some studies have found that most of the genes involved in the regulation of ferroptosis or act as markers o...

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Autores principales: He, Zhixian, Zhou, Zuoyuan, Wang, Feiran, Gai, Ling, Huang, Yeqing, Zhong, Xiang, Li, Jing, Zuo, Ling, Zhang, Nannan, Ni, Sujie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403941/
https://www.ncbi.nlm.nih.gov/pubmed/36035010
http://dx.doi.org/10.21037/atm-22-3736
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author He, Zhixian
Zhou, Zuoyuan
Wang, Feiran
Gai, Ling
Huang, Yeqing
Zhong, Xiang
Li, Jing
Zuo, Ling
Zhang, Nannan
Ni, Sujie
author_facet He, Zhixian
Zhou, Zuoyuan
Wang, Feiran
Gai, Ling
Huang, Yeqing
Zhong, Xiang
Li, Jing
Zuo, Ling
Zhang, Nannan
Ni, Sujie
author_sort He, Zhixian
collection PubMed
description BACKGROUND: Ferroptosis is a kind of programmed cell death that is characterized by iron dependence. It differs from apoptosis, necrosis, autophagy, pyroptosis, and other types of cell death. Some studies have found that most of the genes involved in the regulation of ferroptosis or act as markers of ferroptosis are related to the poor prognosis of cancer patients. METHODS: This study evaluated the expression, mutation, and copy number variation (CNV) of 60 previously reported ferroptosis genes in breast cancer samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Unsupervised clustering of breast cancer samples with ferroptosis genes was performed, followed by enrichment analysis with Gene Set Variation Analysis (GSVA), mutation display, and correlation analysis of clinical characteristics. Based on the analysis of differences among groups, the ferroptosis-related genes were identified, and the consistent clustering of breast cancer samples was performed. The characteristic genes were screened by stochastic forest algorithm and COX analysis, and a ferroptosis score (ferr.score) model was constructed to evaluate the prognosis of breast cancer patients. RESULTS: Copy number amplification and deletion of ferroptosis genes are common in breast cancer. Breast cancer patients grouped by ferroptosis gene clusters showed significant differences in survival, immune cell infiltration, and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. The ferroptosis-related differential genes were identified by comparison among clustering groups of ferroptosis gene. Characteristic genes were screened from these ferroptosis-related differential genes to construct the ferr.score model. The scoring model could accurately distinguish and predict the survival prognosis and immunotherapy efficacy in breast cancer patients. CONCLUSIONS: Ferroptosis plays an important role in the occurrence and development of tumors. According to the ferr.score model, the breast cancer samples can be divided into two groups with significantly different prognoses. These results provide novel insights and ideas for immunotherapy in breast cancer patients.
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spelling pubmed-94039412022-08-26 Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer He, Zhixian Zhou, Zuoyuan Wang, Feiran Gai, Ling Huang, Yeqing Zhong, Xiang Li, Jing Zuo, Ling Zhang, Nannan Ni, Sujie Ann Transl Med Original Article BACKGROUND: Ferroptosis is a kind of programmed cell death that is characterized by iron dependence. It differs from apoptosis, necrosis, autophagy, pyroptosis, and other types of cell death. Some studies have found that most of the genes involved in the regulation of ferroptosis or act as markers of ferroptosis are related to the poor prognosis of cancer patients. METHODS: This study evaluated the expression, mutation, and copy number variation (CNV) of 60 previously reported ferroptosis genes in breast cancer samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Unsupervised clustering of breast cancer samples with ferroptosis genes was performed, followed by enrichment analysis with Gene Set Variation Analysis (GSVA), mutation display, and correlation analysis of clinical characteristics. Based on the analysis of differences among groups, the ferroptosis-related genes were identified, and the consistent clustering of breast cancer samples was performed. The characteristic genes were screened by stochastic forest algorithm and COX analysis, and a ferroptosis score (ferr.score) model was constructed to evaluate the prognosis of breast cancer patients. RESULTS: Copy number amplification and deletion of ferroptosis genes are common in breast cancer. Breast cancer patients grouped by ferroptosis gene clusters showed significant differences in survival, immune cell infiltration, and enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. The ferroptosis-related differential genes were identified by comparison among clustering groups of ferroptosis gene. Characteristic genes were screened from these ferroptosis-related differential genes to construct the ferr.score model. The scoring model could accurately distinguish and predict the survival prognosis and immunotherapy efficacy in breast cancer patients. CONCLUSIONS: Ferroptosis plays an important role in the occurrence and development of tumors. According to the ferr.score model, the breast cancer samples can be divided into two groups with significantly different prognoses. These results provide novel insights and ideas for immunotherapy in breast cancer patients. AME Publishing Company 2022-08 /pmc/articles/PMC9403941/ /pubmed/36035010 http://dx.doi.org/10.21037/atm-22-3736 Text en 2022 Annals of Translational Medicine. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
He, Zhixian
Zhou, Zuoyuan
Wang, Feiran
Gai, Ling
Huang, Yeqing
Zhong, Xiang
Li, Jing
Zuo, Ling
Zhang, Nannan
Ni, Sujie
Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
title Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
title_full Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
title_fullStr Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
title_full_unstemmed Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
title_short Comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
title_sort comprehensive analysis of the relationship between the ferroptosis and tumor-infiltrating immune cells, mutation, and immunotherapy in breast cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403941/
https://www.ncbi.nlm.nih.gov/pubmed/36035010
http://dx.doi.org/10.21037/atm-22-3736
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