Cargando…

m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment

BACKGROUND: We analyzed the n6-methyladenosine (m6A) modification patterns of immune cells infiltrating the tumor microenvironment of breast cancer (BC) to provide a new perspective for the early diagnosis and treatment of BC. METHODS: Based on 23 m6A regulatory factors, we identified m6A-related ge...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Fei, Yu, Xiaopeng, He, Guijin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566073/
https://www.ncbi.nlm.nih.gov/pubmed/34745261
http://dx.doi.org/10.1155/2021/9987376
_version_ 1784593936850878464
author Liu, Fei
Yu, Xiaopeng
He, Guijin
author_facet Liu, Fei
Yu, Xiaopeng
He, Guijin
author_sort Liu, Fei
collection PubMed
description BACKGROUND: We analyzed the n6-methyladenosine (m6A) modification patterns of immune cells infiltrating the tumor microenvironment of breast cancer (BC) to provide a new perspective for the early diagnosis and treatment of BC. METHODS: Based on 23 m6A regulatory factors, we identified m6A-related gene characteristics and m6A modification patterns in BC through unsupervised cluster analysis. To examine the differences in biological processes among various m6A modification modes, we performed genomic variation analysis. We then quantified the relative infiltration levels of different immune cell subpopulations in the tumor microenvironment of BC using the CIBERSORT algorithm and single-sample gene set enrichment analysis. Univariate Cox analysis was used to screen for m6A characteristic genes related to prognosis. Finally, we evaluated the m6A modification pattern of patients with a single BC by constructing the m6Ascore based on principal component analysis. RESULTS: We identified three different m6A modification patterns in 2128 BC samples. A higher abundance of the immune infiltration of the m6Acluster C was indicated by the results of CIBERSORT and the single-sample gene set enrichment analysis. Based on the m6A characteristic genes obtained through screening, the m6Ascore was determined. The BC patients were segregated into m6Ascore groups of low and high categories, which revealed significant survival benefits among patients with low m6Ascores. Additionally, the high-m6Ascore group had a higher mutation frequency and was associated with low PD-L1 expression, and the m6Ascore and tumor mutation burden showed a positive correlation. In addition, treatment effects were better in patients in the high-m6Ascore group. CONCLUSIONS: In case of a single patient with BC, the immune cell infiltration characteristics of the tumor microenvironment and the m6A methylation modification pattern could be evaluated using the m6Ascore. Our results provide a foundation for improving personalized immunotherapy of BC.
format Online
Article
Text
id pubmed-8566073
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-85660732021-11-04 m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment Liu, Fei Yu, Xiaopeng He, Guijin J Oncol Research Article BACKGROUND: We analyzed the n6-methyladenosine (m6A) modification patterns of immune cells infiltrating the tumor microenvironment of breast cancer (BC) to provide a new perspective for the early diagnosis and treatment of BC. METHODS: Based on 23 m6A regulatory factors, we identified m6A-related gene characteristics and m6A modification patterns in BC through unsupervised cluster analysis. To examine the differences in biological processes among various m6A modification modes, we performed genomic variation analysis. We then quantified the relative infiltration levels of different immune cell subpopulations in the tumor microenvironment of BC using the CIBERSORT algorithm and single-sample gene set enrichment analysis. Univariate Cox analysis was used to screen for m6A characteristic genes related to prognosis. Finally, we evaluated the m6A modification pattern of patients with a single BC by constructing the m6Ascore based on principal component analysis. RESULTS: We identified three different m6A modification patterns in 2128 BC samples. A higher abundance of the immune infiltration of the m6Acluster C was indicated by the results of CIBERSORT and the single-sample gene set enrichment analysis. Based on the m6A characteristic genes obtained through screening, the m6Ascore was determined. The BC patients were segregated into m6Ascore groups of low and high categories, which revealed significant survival benefits among patients with low m6Ascores. Additionally, the high-m6Ascore group had a higher mutation frequency and was associated with low PD-L1 expression, and the m6Ascore and tumor mutation burden showed a positive correlation. In addition, treatment effects were better in patients in the high-m6Ascore group. CONCLUSIONS: In case of a single patient with BC, the immune cell infiltration characteristics of the tumor microenvironment and the m6A methylation modification pattern could be evaluated using the m6Ascore. Our results provide a foundation for improving personalized immunotherapy of BC. Hindawi 2021-10-27 /pmc/articles/PMC8566073/ /pubmed/34745261 http://dx.doi.org/10.1155/2021/9987376 Text en Copyright © 2021 Fei Liu et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Liu, Fei
Yu, Xiaopeng
He, Guijin
m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment
title m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment
title_full m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment
title_fullStr m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment
title_full_unstemmed m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment
title_short m6A-Mediated Tumor Invasion and Methylation Modification in Breast Cancer Microenvironment
title_sort m6a-mediated tumor invasion and methylation modification in breast cancer microenvironment
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8566073/
https://www.ncbi.nlm.nih.gov/pubmed/34745261
http://dx.doi.org/10.1155/2021/9987376
work_keys_str_mv AT liufei m6amediatedtumorinvasionandmethylationmodificationinbreastcancermicroenvironment
AT yuxiaopeng m6amediatedtumorinvasionandmethylationmodificationinbreastcancermicroenvironment
AT heguijin m6amediatedtumorinvasionandmethylationmodificationinbreastcancermicroenvironment