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pmid:32373154

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

Yanshen Kuang · Ying Wang · Wanli Zhai · Xuning Wang · Bingdong Zhang · Maolin Xu · Shaohua Guo · Mu Ke · Baoqing Jia · Hongyi Liu

Frontiers in genetics · 2020 doi:10.3389/fgene.2020.00301

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title
Genome-Wide Analysis of Methylation-Driven Genes and Identification of an Eight-Gene Panel for Prognosis Prediction in Breast Cancer.
doi
10.3389/fgene.2020.00301
pmid
32373154
authors array · 10 items
[0]
Yanshen Kuang
[1]
Ying Wang
[2]
Wanli Zhai
[3]
Xuning Wang
[4]
Bingdong Zhang
[5]
Maolin Xu
[6]
Shaohua Guo
[7]
Mu Ke
[8]
Baoqing Jia
[9]
Hongyi Liu
journal
Frontiers in genetics
year
2020
abstract
BACKGROUND: Aberrant 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. METHODS: DNA 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. RESULTS: A 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. CONCLUSIONS: Our 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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We next performed integrative analysis with the MethylMix package. Data of BC patients in the TCGA project (TCGA-BRCA) were downloaded. Level 1 (Raw data) clinical characteristics data were obtained from TCGA via GDC Xena Hub (Goldman et al., 2019) (Version GDC Release 10.0). Level 2 (Normalized data) Infinium HumanMethylation450K(HM450K) methylation data (β-value calculations for each probe and sample) were obtained from TCGA via GDC Xena Hub (Version GDC Release 10.0). Level 3 (Aggregated data) gene expression data were obtained from TCGA via Firehose.
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sections[5] "Integrative Analysis" paragraph 2
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We next performed integrative analysis with the MethylMix package.
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sections[3] "Data Acquisition" paragraph 2
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Data of BC patients in the TCGA project (TCGA-BRCA) were downloaded.
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sections[3] "Data Acquisition" paragraph 3
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Level 1 (Raw data) clinical characteristics data were obtained from TCGA via GDC Xena Hub (Goldman et al., 2019) (Version GDC Release 10.0).
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sections[3] "Data Acquisition" paragraph 4
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Level 2 (Normalized data) Infinium HumanMethylation450K(HM450K) methylation data (β-value calculations for each probe and sample) were obtained from TCGA via GDC Xena Hub (Version GDC Release 10.0).
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Level 3 (Aggregated data) gene expression data were obtained from TCGA via Firehose.
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The data sets generated and analyzed during the current study are publicly available in the TCGA repository (https://portal.gdc.cancer.gov/) and GEO database (under accession code: GSE72308).
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The data sets generated and analyzed during the current study are publicly available in the TCGA repository (https://portal.gdc.cancer.gov/) and GEO database (under accession code: GSE72308).
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We next performed integrative analysis with the MethylMix package. Data of BC patients in the TCGA project (TCGA-BRCA) were downloaded. Level 1 (Raw data) clinical characteristics data were obtained from TCGA via GDC Xena Hub (Goldman et al., 2019) (Version GDC Release 10.0). Level 2 (Normalized data) Infinium HumanMethylation450K(HM450K) methylation data (β-value calculations for each probe and sample) were obtained from TCGA via GDC Xena Hub (Version GDC Release 10.0). Level 3 (Aggregated data) gene expression data were obtained from TCGA via Firehose.
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lineage object · 4 fields
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f2132e96ae6c7a4e
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assay:1
Complete file
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The present study aimed to identify a novel methylation-based prognosis biomarker panel by integrally analyzing gene expression and methylation patterns in BC patients.\nMETHODS: DNA 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.\nRESULTS: A 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.\nCONCLUSIONS: Our 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.", "claims": [{"id": "claim-method", "statement": "We next performed integrative analysis with the MethylMix package. Data of BC patients in the TCGA project (TCGA-BRCA) were downloaded. Level 1 (Raw data) clinical characteristics data were obtained from TCGA via GDC Xena Hub (Goldman et al., 2019) (Version GDC Release 10.0). Level 2 (Normalized data) Infinium HumanMethylation450K(HM450K) methylation data (β-value calculations for each probe and sample) were obtained from TCGA via GDC Xena Hub (Version GDC Release 10.0). 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