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胃肠道腺癌分析确定了基于启动子甲基化的癌症亚型和特征。

Gastrointestinal adenocarcinoma analysis identifies promoter methylation-based cancer subtypes and signatures.

机构信息

Department of Gastrointestinal Surgery II, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, China.

The Central Laboratory of the First Clinical College of Wuhan University, Wuhan, 430060, Hubei Province, China.

出版信息

Sci Rep. 2020 Dec 4;10(1):21234. doi: 10.1038/s41598-020-78228-y.

DOI:10.1038/s41598-020-78228-y
PMID:33277583
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7719188/
Abstract

Gastric adenocarcinoma (GAC) and colon adenocarcinoma (CAC) are the most common gastrointestinal cancer subtypes, with a high incidence and mortality. Numerous studies have shown that its occurrence and progression are significantly related to abnormal DNA methylation, especially CpG island methylation. However, little is known about the application of DNA methylation in GAC and CAC. The methylation profiles were accessed from the Cancer Genome Atlas database to identify promoter methylation-based cancer subtypes and signatures for GAC and CAC. Six hypo-methylated clusters for GAC and six hyper-methylated clusters for CAC were separately generated with different OS profiles, tumor progression became worse as the methylation level decreased in GAC or increased in CAC, and hypomethylation in GAC and hypermethylation in CAC were negatively correlated with microsatellite instability. Additionally, the hypo- and hyper-methylated site-based signatures with high accuracy, high efficiency and strong independence can separately predict the OS of GAC and CAC patients. By integrating the methylation-based signatures with prognosis-related clinicopathologic characteristics, two clinicopathologic-epigenetic nomograms were cautiously established with strong predictive performance and high accuracy. Our research indicates that methylation mechanisms differ between GAC and CAC, and provides novel clinical biomarkers for the diagnosis and treatment of GAC and CAC.

摘要

胃腺癌（Gastric adenocarcinoma，GAC）和结肠腺癌（Colon adenocarcinoma，CAC）是最常见的胃肠道癌症亚型，具有较高的发病率和死亡率。大量研究表明，其发生和发展与异常的 DNA 甲基化密切相关，尤其是 CpG 岛甲基化。然而，关于 DNA 甲基化在 GAC 和 CAC 中的应用知之甚少。本研究从癌症基因组图谱（Cancer Genome Atlas，TCGA）数据库中获取甲基化谱，以确定基于启动子甲基化的 GAC 和 CAC 癌症亚型和特征。分别生成了 6 个 GAC 低甲基化簇和 6 个 CAC 高甲基化簇，它们具有不同的 OS 谱，随着 GAC 中甲基化水平降低或 CAC 中甲基化水平升高，肿瘤进展变得更糟，GAC 中的低甲基化和 CAC 中的高甲基化与微卫星不稳定性呈负相关。此外，基于低甲基化和高甲基化位点的具有高准确性、高效率和强独立性的特征分别可以预测 GAC 和 CAC 患者的 OS。通过将基于甲基化的特征与预后相关的临床病理特征相结合，谨慎地建立了两个具有较强预测性能和高准确性的临床病理 - 表观遗传列线图。我们的研究表明，GAC 和 CAC 之间的甲基化机制不同，为 GAC 和 CAC 的诊断和治疗提供了新的临床生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/fcad59269f21/41598_2020_78228_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/b509c01b9ac0/41598_2020_78228_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/c372e07926eb/41598_2020_78228_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/d95ed0e1bfba/41598_2020_78228_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/daf7908d5298/41598_2020_78228_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/5a1fe004a19b/41598_2020_78228_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/a6b7042da92b/41598_2020_78228_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/3c1ef7191542/41598_2020_78228_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/fcad59269f21/41598_2020_78228_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/b509c01b9ac0/41598_2020_78228_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/c372e07926eb/41598_2020_78228_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/d95ed0e1bfba/41598_2020_78228_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/daf7908d5298/41598_2020_78228_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/5a1fe004a19b/41598_2020_78228_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/a6b7042da92b/41598_2020_78228_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/3c1ef7191542/41598_2020_78228_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a5d6/7719188/fcad59269f21/41598_2020_78228_Fig8_HTML.jpg

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