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乳腺癌中甲基化驱动基因的全基因组分析及用于预后预测的八基因panel的鉴定

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

作者信息

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

机构信息

Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

State Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, Beijing, China.

出版信息

Front Genet. 2020 Apr 21;11:301. doi: 10.3389/fgene.2020.00301. eCollection 2020.

DOI:10.3389/fgene.2020.00301
PMID:32373154
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7186397/
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.

摘要

背景

异常的DNA甲基化是一种关键的表观遗传调节因子，与包括乳腺癌（BC）在内的各种癌症的发生和发展密切相关。本研究旨在通过综合分析BC患者的基因表达和甲基化模式，鉴定一种基于甲基化的新型预后生物标志物panel。

方法

从癌症基因组图谱（TCGA）下载乳腺癌（BRCA）的DNA甲基化和基因表达数据。应用包括ChAMP、SVA和MethylMix在内的R包来鉴定独特的甲基化驱动基因。随后，将这些基因进行Metascape的GO分析。采用单变量Cox回归在甲基化驱动基因中鉴定生存相关基因。应用基于稳健似然的生存模型来定义预后标志物。使用独立数据集（GSE72308）进一步验证我们的风险评分系统。

结果

从765例BC患者中鉴定出总共879个DNA甲基化驱动基因。在发现队列中，我们鉴定出50个生存相关的甲基化驱动基因。最后，我们构建了一个由八个甲基化驱动基因组成的panel作为预后预测指标。

结论

我们对与BC患者生存状态相关的转录组和甲基化组变异的分析，进一步加深了对基本生物学过程的理解，并为BC的遗传病因提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/832ee9b1702b/fgene-11-00301-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/00a89be20b79/fgene-11-00301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/e2b1e41390c9/fgene-11-00301-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/dbced4620e0b/fgene-11-00301-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/0b2a4510c6a6/fgene-11-00301-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/bb6564ad52e0/fgene-11-00301-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/0a296845169d/fgene-11-00301-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/afcbf98f7a40/fgene-11-00301-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/832ee9b1702b/fgene-11-00301-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/00a89be20b79/fgene-11-00301-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/e2b1e41390c9/fgene-11-00301-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/dbced4620e0b/fgene-11-00301-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/0b2a4510c6a6/fgene-11-00301-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/bb6564ad52e0/fgene-11-00301-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/0a296845169d/fgene-11-00301-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/afcbf98f7a40/fgene-11-00301-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f1d/7186397/832ee9b1702b/fgene-11-00301-g008.jpg

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