m6A RNA Methylation Regulator YTHDF1 Correlated With Immune Microenvironment Predicts Clinical Outcomes and Therapeutic Efficacy in Breast Cancer
Objective: Increasing evidence highlights the roles of N 6 -methyladenosine (m 6 A) and its regulators in oncogenesis. Herein, this study observed the associations of m 6 A regulators with breast cancer. Methods: RNA-seq profiles of breast cancer were retrieved from the Cancer Genome Atlas (TCGA) da...
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Published in | Frontiers in medicine Vol. 8; p. 667543 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Frontiers Media S.A
09.08.2021
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Subjects | |
Online Access | Get full text |
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Summary: | Objective:
Increasing evidence highlights the roles of N
6
-methyladenosine (m
6
A) and its regulators in oncogenesis. Herein, this study observed the associations of m
6
A regulators with breast cancer.
Methods:
RNA-seq profiles of breast cancer were retrieved from the Cancer Genome Atlas (TCGA) database. The expression of m
6
A regulators was analyzed in tumor and normal tissues. Their expression correlations were analyzed by Spearson test. Overall survival (OS) analysis of these regulators was then presented. Gene set enrichment analysis (GSEA) was performed in high and low YTHDF1 expression groups. The correlations of YTHDF1 expression with immune cells and tumor mutation burden (TMB) were calculated in breast cancer samples. Somatic variation was assessed in high and low YTHDF1 expression groups.
Results:
Most of m
6
A regulators were abnormally expressed in breast cancer compared to normal tissues. At the mRNA levels, there were closely relationships between them. Among them, YTHDF1 up-regulation was significantly related to undesirable prognosis (
p
= 0.025). GSEA results showed that high YTHDF1 expression was associated with cancer-related pathways. Furthermore, YTHDF1 expression was significantly correlated with T cells CD4 memory activated, NK cells activated, monocytes, and macrophages. There were higher TMB scores in YTHDF1 up-regulation group than its down-regulation group. Missense mutation and non-sense mutation were the most frequent mutation types.
Conclusion:
Our findings suggested that dysregulated m
6
A regulator YTHDF1 was predictive of survival outcomes as well as response to immunotherapy of breast cancer, and were closely related to immune microenvironment. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Huabing Li, Shanghai Jiao Tong University School of Medicine, China; Robert Sebra, Icahn School of Medicine at Mount Sinai, United States These authors have contributed equally to this work This article was submitted to Precision Medicine, a section of the journal Frontiers in Medicine Edited by: Fu Wang, Xi'an Jiaotong University, China |
ISSN: | 2296-858X 2296-858X |
DOI: | 10.3389/fmed.2021.667543 |