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甲基化和转录组的多组学分析揭示了食管癌中的一种新特征。

Multiomic Analysis of Methylation and Transcriptome Reveals a Novel Signature in Esophageal Cancer.

作者信息

Jin Yi-Qi, Miao Dong-Liu

机构信息

Department of Intervention and Vascular Surgery, Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, Jiangsu, China.

出版信息

Dose Response. 2020 Jul 15;18(3):1559325820942075. doi: 10.1177/1559325820942075. eCollection 2020 Jul-Sep.

DOI:10.1177/1559325820942075
PMID:32728353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7364835/
Abstract

BACKGROUND

Epigenetic alterations have been shown to lead to human carcinogenesis. The aim of this study was to perform an integrative analysis to develop an epigenetic signature to predict overall survival (OS) of esophageal cancer.

METHODS

DNA methylation and messenger RNA expression data of esophageal cancer samples were downloaded from The Cancer Genome Atlas database and were incorporated and analyzed using an R package MethylMix. Functional enrichment analysis of the methylation-related differentially expressed genes (DEGs) was performed. Epigenetic signature and nomogram associated with the OS of esophageal cancer were established by the multivariate Cox model.

RESULTS

A total of 71 methylation-related DEGs were identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that these genes were involved in the biological process related to the initiation and progression of esophageal cancer. Two-gene (FAM24B and FAM200A) risk signature for OS was developed by multivariate Cox analysis, of which had high accuracy. The signature is independent of clinicopathological variables and indicated better predictive power than other clinicopathological variables. Moreover, we developed a novel prognostic nomogram based on risk score and 3 clinicopathological factors.

CONCLUSIONS

Our study indicated possible methylation-related DEGs and established an epigenetic signature, which may provide novel insights for understanding the pathogenesis of esophageal cancer.

摘要

背景

表观遗传改变已被证明可导致人类致癌。本研究的目的是进行综合分析，以开发一种表观遗传特征来预测食管癌的总生存期（OS）。

方法

从癌症基因组图谱数据库下载食管癌样本的DNA甲基化和信使RNA表达数据，并使用R包MethylMix进行整合和分析。对甲基化相关差异表达基因（DEG）进行功能富集分析。通过多变量Cox模型建立与食管癌OS相关的表观遗传特征和列线图。

结果

共鉴定出71个甲基化相关的DEG。京都基因与基因组百科全书通路分析表明，这些基因参与了与食管癌发生和进展相关的生物学过程。通过多变量Cox分析建立了用于OS的双基因（FAM24B和FAM200A）风险特征，其具有较高的准确性。该特征独立于临床病理变量，并且比其他临床病理变量具有更好的预测能力。此外，我们基于风险评分和3个临床病理因素开发了一种新的预后列线图。

结论

我们的研究表明了可能的甲基化相关DEG，并建立了一种表观遗传特征，这可能为理解食管癌的发病机制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/b7aba7750297/10.1177_1559325820942075-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/c14401329adf/10.1177_1559325820942075-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/f3b809c752b5/10.1177_1559325820942075-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/ba43bf75ea2d/10.1177_1559325820942075-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/76af763c8fdc/10.1177_1559325820942075-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/7452ada685f8/10.1177_1559325820942075-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/79900a45b1e9/10.1177_1559325820942075-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/1411baa0a219/10.1177_1559325820942075-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/b7aba7750297/10.1177_1559325820942075-fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/c14401329adf/10.1177_1559325820942075-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/f3b809c752b5/10.1177_1559325820942075-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/ba43bf75ea2d/10.1177_1559325820942075-fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/76af763c8fdc/10.1177_1559325820942075-fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/7452ada685f8/10.1177_1559325820942075-fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/79900a45b1e9/10.1177_1559325820942075-fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/1411baa0a219/10.1177_1559325820942075-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0318/7364835/b7aba7750297/10.1177_1559325820942075-fig8.jpg

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