RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer
RNA N6-methyladenosine (m6A) methylation is the most prevalent epitranscriptomic modification in mammals, with a complex and fine-tuning regulatory system. Recent studies have illuminated the potential of m6A regulators in clinical applications including diagnosis, therapeutics, and prognosis. Based...
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doaj-7dd015be2d424436a6d8bc5c8810074d2021-01-29T05:33:55ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-01-011010.3389/fonc.2020.611191611191RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast CancerLin Yang0Lin Yang1Lin Yang2Shuangling Wu3Chunhui Ma4Chunhui Ma5Chunhui Ma6Shuhui Song7Shuhui Song8Feng Jin9Yamei Niu10Yamei Niu11Yamei Niu12Wei-Min Tong13Wei-Min Tong14Wei-Min Tong15Department of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Basic Medicine, Peking Union Medical College, Beijing, ChinaMolecular Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Basic Medicine, Peking Union Medical College, Beijing, ChinaMolecular Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, ChinaChina National Center for Bioinformation, Beijing, ChinaNational Genomics Data Center & CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, ChinaDepartment of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, ChinaDepartment of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Basic Medicine, Peking Union Medical College, Beijing, ChinaMolecular Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Pathology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, ChinaSchool of Basic Medicine, Peking Union Medical College, Beijing, ChinaMolecular Pathology Research Center, Chinese Academy of Medical Sciences, Beijing, ChinaRNA N6-methyladenosine (m6A) methylation is the most prevalent epitranscriptomic modification in mammals, with a complex and fine-tuning regulatory system. Recent studies have illuminated the potential of m6A regulators in clinical applications including diagnosis, therapeutics, and prognosis. Based on six datasets of breast cancer in The Cancer Genome Atlas (TCGA) database and two additional proteomic datasets, we provide a comprehensive view of all the known m6A regulators in their gene expression, copy number variations (CNVs), DNA methylation status, and protein levels in breast tumors and their association with prognosis. Among four breast cancer subtypes, basal-like subtype exhibits distinct expression and genomic alteration in m6A regulators from other subtypes. Accordingly, four representative regulators (IGF2BP2, IGF2BP3, YTHDC2, and RBM15) are identified as basal-like subtype-featured genes. Notably, luminal A/B samples are subclassified into two clusters based on the methylation status of those four genes. In line with its similarity to basal-like subtype, cluster1 shows upregulation in immune-related genes and cell adhesion molecules, as well as an increased number of tumor-infiltrating lymphocytes. Besides, cluster1 has worse disease-free and progression-free survival, especially among patients diagnosed with stage II and luminal B subtype. Together, this study highlights the potential functions of m6A regulators in the occurrence and malignancy progression of breast cancer. Given the heterogeneity within luminal subtype and high risk of recurrence and metastasis in a portion of patients, the prognostic stratification of luminal A/B subtypes utilizing basal-featured m6A regulators may help to improve the accuracy of diagnosis and therapeutics of breast cancer.https://www.frontiersin.org/articles/10.3389/fonc.2020.611191/fullRNA methylationm6A regulatorsgenomic regulationbreast cancer subtypessubclassificationsurvival |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lin Yang Lin Yang Lin Yang Shuangling Wu Chunhui Ma Chunhui Ma Chunhui Ma Shuhui Song Shuhui Song Feng Jin Yamei Niu Yamei Niu Yamei Niu Wei-Min Tong Wei-Min Tong Wei-Min Tong |
spellingShingle |
Lin Yang Lin Yang Lin Yang Shuangling Wu Chunhui Ma Chunhui Ma Chunhui Ma Shuhui Song Shuhui Song Feng Jin Yamei Niu Yamei Niu Yamei Niu Wei-Min Tong Wei-Min Tong Wei-Min Tong RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer Frontiers in Oncology RNA methylation m6A regulators genomic regulation breast cancer subtypes subclassification survival |
author_facet |
Lin Yang Lin Yang Lin Yang Shuangling Wu Chunhui Ma Chunhui Ma Chunhui Ma Shuhui Song Shuhui Song Feng Jin Yamei Niu Yamei Niu Yamei Niu Wei-Min Tong Wei-Min Tong Wei-Min Tong |
author_sort |
Lin Yang |
title |
RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer |
title_short |
RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer |
title_full |
RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer |
title_fullStr |
RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer |
title_full_unstemmed |
RNA m6A Methylation Regulators Subclassify Luminal Subtype in Breast Cancer |
title_sort |
rna m6a methylation regulators subclassify luminal subtype in breast cancer |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Oncology |
issn |
2234-943X |
publishDate |
2021-01-01 |
description |
RNA N6-methyladenosine (m6A) methylation is the most prevalent epitranscriptomic modification in mammals, with a complex and fine-tuning regulatory system. Recent studies have illuminated the potential of m6A regulators in clinical applications including diagnosis, therapeutics, and prognosis. Based on six datasets of breast cancer in The Cancer Genome Atlas (TCGA) database and two additional proteomic datasets, we provide a comprehensive view of all the known m6A regulators in their gene expression, copy number variations (CNVs), DNA methylation status, and protein levels in breast tumors and their association with prognosis. Among four breast cancer subtypes, basal-like subtype exhibits distinct expression and genomic alteration in m6A regulators from other subtypes. Accordingly, four representative regulators (IGF2BP2, IGF2BP3, YTHDC2, and RBM15) are identified as basal-like subtype-featured genes. Notably, luminal A/B samples are subclassified into two clusters based on the methylation status of those four genes. In line with its similarity to basal-like subtype, cluster1 shows upregulation in immune-related genes and cell adhesion molecules, as well as an increased number of tumor-infiltrating lymphocytes. Besides, cluster1 has worse disease-free and progression-free survival, especially among patients diagnosed with stage II and luminal B subtype. Together, this study highlights the potential functions of m6A regulators in the occurrence and malignancy progression of breast cancer. Given the heterogeneity within luminal subtype and high risk of recurrence and metastasis in a portion of patients, the prognostic stratification of luminal A/B subtypes utilizing basal-featured m6A regulators may help to improve the accuracy of diagnosis and therapeutics of breast cancer. |
topic |
RNA methylation m6A regulators genomic regulation breast cancer subtypes subclassification survival |
url |
https://www.frontiersin.org/articles/10.3389/fonc.2020.611191/full |
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