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Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer

The N(6)-methyladenosine (m(6)A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m(6)A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In thi...

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Autores principales: Zhao, Guanghui, An, Junhua, Pu, Qian, Geng, Wenwen, Song, Haiyun, Zhao, Qianqian, Gao, Haidong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600443/
https://www.ncbi.nlm.nih.gov/pubmed/34804948
http://dx.doi.org/10.3389/fonc.2021.756412
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author Zhao, Guanghui
An, Junhua
Pu, Qian
Geng, Wenwen
Song, Haiyun
Zhao, Qianqian
Gao, Haidong
author_facet Zhao, Guanghui
An, Junhua
Pu, Qian
Geng, Wenwen
Song, Haiyun
Zhao, Qianqian
Gao, Haidong
author_sort Zhao, Guanghui
collection PubMed
description The N(6)-methyladenosine (m(6)A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m(6)A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this study, we comprehensively evaluated the genetic variations and transcript expressions of 15 m(6)A regulators in 1,079 breast cancer samples from the Cancer Genome Atlas (TCGA) database. We validated major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal tissues from 39 pairs of clinical breast cancer samples with different molecular subtypes, and especially high expression of m(6)A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m(6)A regulators’ pattern showed distinct overall survival, immune activation status, and immune cell infiltration, and clinical samples confirmed the diversity of lymphocytic infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes, it suggested that m(6)A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m(6)A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m(6)A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy.
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spelling pubmed-86004432021-11-19 Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer Zhao, Guanghui An, Junhua Pu, Qian Geng, Wenwen Song, Haiyun Zhao, Qianqian Gao, Haidong Front Oncol Oncology The N(6)-methyladenosine (m(6)A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m(6)A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this study, we comprehensively evaluated the genetic variations and transcript expressions of 15 m(6)A regulators in 1,079 breast cancer samples from the Cancer Genome Atlas (TCGA) database. We validated major regulators had significantly differential mRNA and protein expression in tumor tissue compared to normal tissues from 39 pairs of clinical breast cancer samples with different molecular subtypes, and especially high expression of m(6)A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m(6)A regulators’ pattern showed distinct overall survival, immune activation status, and immune cell infiltration, and clinical samples confirmed the diversity of lymphocytic infiltration. The profiles of these two clusters accorded with that of two classical cancer-immune phenotypes, immune-excluded and immune-inflamed phenotypes, it suggested that m(6)A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m(6)A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m(6)A modification pattern will contribute to enhance our understanding of the characterization of immune cell infiltration in the tumor microenvironment and promote the responsiveness of breast cancer to immunotherapy. Frontiers Media S.A. 2021-11-04 /pmc/articles/PMC8600443/ /pubmed/34804948 http://dx.doi.org/10.3389/fonc.2021.756412 Text en Copyright © 2021 Zhao, An, Pu, Geng, Song, Zhao and Gao 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 Oncology
Zhao, Guanghui
An, Junhua
Pu, Qian
Geng, Wenwen
Song, Haiyun
Zhao, Qianqian
Gao, Haidong
Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer
title Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer
title_full Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer
title_fullStr Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer
title_full_unstemmed Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer
title_short Gene Signatures and Cancer-Immune Phenotypes Based on m(6)A Regulators in Breast Cancer
title_sort gene signatures and cancer-immune phenotypes based on m(6)a regulators in breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600443/
https://www.ncbi.nlm.nih.gov/pubmed/34804948
http://dx.doi.org/10.3389/fonc.2021.756412
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