Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer

BackgroundAberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expres...

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Main Authors: Yanshen Kuang, Ying Wang, Wanli Zhai, Xuning Wang, Bingdong Zhang, Maolin Xu, Shaohua Guo, Mu Ke, Baoqing Jia, Hongyi Liu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-04-01
Series:Frontiers in Genetics
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fgene.2020.00301/full
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author Yanshen Kuang
Ying Wang
Wanli Zhai
Xuning Wang
Bingdong Zhang
Maolin Xu
Shaohua Guo
Mu Ke
Baoqing Jia
Hongyi Liu
author_facet Yanshen Kuang
Ying Wang
Wanli Zhai
Xuning Wang
Bingdong Zhang
Maolin Xu
Shaohua Guo
Mu Ke
Baoqing Jia
Hongyi Liu
author_sort Yanshen Kuang
collection DOAJ
description BackgroundAberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients.MethodsDNA methylation and gene expression data of breast cancer (BRCA) were downloaded from The Cancer Genome Atlas (TCGA). R packages, including ChAMP, SVA, and MethylMix, were applied to identify the unique methylation-driven genes. Subsequently, these genes were subjected to Metascape for GO analysis. Univariant Cox regression was used to identify survival-related genes among the methylation-driven genes. Robust likelihood-based survival modeling was applied to define the prognosis markers. An independent data set (GSE72308) was used for further validation of our risk score system.ResultsA total of 879 DNA methylation-driven genes were identified from 765 BC patients. In the discovery cohort, we identified 50 survival-related methylation-driven genes. Finally, we built an eight-methylation-driven gene panel that serves as prognostic predictors.ConclusionsOur analysis of transcriptome and methylome variations associated with the survival status of BC patients provides a further understanding of basic biological processes and a basis for the genetic etiology in BC.
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spelling doaj.art-e5f87a0c065c418f8240607c9c4f7b222022-12-22T02:37:34ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-04-011110.3389/fgene.2020.00301523056Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast CancerYanshen Kuang0Ying Wang1Wanli Zhai2Xuning Wang3Bingdong Zhang4Maolin Xu5Shaohua Guo6Mu Ke7Baoqing Jia8Hongyi Liu9Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaState Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, Beijing, ChinaState Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of General Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaDepartment of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, ChinaBackgroundAberrant DNA methylation is a crucial epigenetic regulator that is closely related to the occurrence and development of various cancers, including breast cancer (BC). The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients.MethodsDNA methylation and gene expression data of breast cancer (BRCA) were downloaded from The Cancer Genome Atlas (TCGA). R packages, including ChAMP, SVA, and MethylMix, were applied to identify the unique methylation-driven genes. Subsequently, these genes were subjected to Metascape for GO analysis. Univariant Cox regression was used to identify survival-related genes among the methylation-driven genes. Robust likelihood-based survival modeling was applied to define the prognosis markers. An independent data set (GSE72308) was used for further validation of our risk score system.ResultsA total of 879 DNA methylation-driven genes were identified from 765 BC patients. In the discovery cohort, we identified 50 survival-related methylation-driven genes. Finally, we built an eight-methylation-driven gene panel that serves as prognostic predictors.ConclusionsOur analysis of transcriptome and methylome variations associated with the survival status of BC patients provides a further understanding of basic biological processes and a basis for the genetic etiology in BC.https://www.frontiersin.org/article/10.3389/fgene.2020.00301/fullepigeneticsDNA methylationbreast cancerprognosis biomarkerintegrative analysis
spellingShingle Yanshen Kuang
Ying Wang
Wanli Zhai
Xuning Wang
Bingdong Zhang
Maolin Xu
Shaohua Guo
Mu Ke
Baoqing Jia
Hongyi Liu
Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer
Frontiers in Genetics
epigenetics
DNA methylation
breast cancer
prognosis biomarker
integrative analysis
title Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer
title_full Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer
title_fullStr Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer
title_full_unstemmed Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer
title_short Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer
title_sort genome wide analysis of methylation driven genes and identification of an eight gene panel for prognosis prediction in breast cancer
topic epigenetics
DNA methylation
breast cancer
prognosis biomarker
integrative analysis
url https://www.frontiersin.org/article/10.3389/fgene.2020.00301/full
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