Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer

The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A RNA methylation modification in tumor immune microenvironment (TIME) of breast cancer are yet fully understood. In this stud...

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Autores principales:	Guanghui Zhao, Junhua An, Qian Pu, Wenwen Geng, Haiyun Song, Qianqian Zhao, Haidong Gao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	breast cancer m6A regulators tumor immune microenvironment prognostic biomarkers immune phenotype Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f76e17925c14411190d8771200e8a873
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spelling	oai:doaj.org-article:f76e17925c14411190d8771200e8a8732021-11-04T10:34:12ZGene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer2234-943X10.3389/fonc.2021.756412https://doaj.org/article/f76e17925c14411190d8771200e8a8732021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.756412/fullhttps://doaj.org/toc/2234-943XThe N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A 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 m6A 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 m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A 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 m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m6A 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.Guanghui ZhaoJunhua AnQian PuWenwen GengHaiyun SongQianqian ZhaoHaidong GaoFrontiers Media S.A.articlebreast cancerm6A regulatorstumor immune microenvironmentprognostic biomarkersimmune phenotypeNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	breast cancer m6A regulators tumor immune microenvironment prognostic biomarkers immune phenotype Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	breast cancer m6A regulators tumor immune microenvironment prognostic biomarkers immune phenotype Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Guanghui Zhao Junhua An Qian Pu Wenwen Geng Haiyun Song Qianqian Zhao Haidong Gao Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer
description	The N6-methyladenosine (m6A) has been considered as a new layer of epitranscriptomic regulation on mRNA processing, stability, and translation. However, potential roles of m6A 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 m6A 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 m6A readers YTHDF1 and YTHDF3 predicted poor survival. Two clusters of breast cancer patients identified by the 15 m6A 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 m6A regulators-based patterns might serve as crucial mediators of TIME in breast cancer. Moreover, the m6A phenotype-related gene signatures could also be survival predictor in breast cancer. Therefore, comprehensive evaluation of tumor m6A 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.
format	article
author	Guanghui Zhao Junhua An Qian Pu Wenwen Geng Haiyun Song Qianqian Zhao Haidong Gao
author_facet	Guanghui Zhao Junhua An Qian Pu Wenwen Geng Haiyun Song Qianqian Zhao Haidong Gao
author_sort	Guanghui Zhao
title	Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer
title_short	Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer
title_full	Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer
title_fullStr	Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer
title_full_unstemmed	Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer
title_sort	gene signatures and cancer-immune phenotypes based on m6a regulators in breast cancer
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/f76e17925c14411190d8771200e8a873
work_keys_str_mv	AT guanghuizhao genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer AT junhuaan genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer AT qianpu genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer AT wenwengeng genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer AT haiyunsong genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer AT qianqianzhao genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer AT haidonggao genesignaturesandcancerimmunephenotypesbasedonm6aregulatorsinbreastcancer
_version_	1718444938607198208

Gene Signatures and Cancer-Immune Phenotypes Based on m6A Regulators in Breast Cancer

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