Multi‐omics analysis reveals epigenetically regulated processes and patient classification in lung adenocarcinoma

Author:

Brativnyk Anastasia1ORCID,Ankill Jørgen12ORCID,Helland Åslaug134ORCID,Fleischer Thomas1ORCID

Affiliation:

1. Department of Cancer Genetics, Institute for Cancer Research Oslo University Hospital Oslo Norway

2. Institute of Clinical Medicine, Faculty of Medicine University of Oslo Oslo Norway

3. Department of Clinical Medicine University of Oslo Oslo Norway

4. Department of Oncology Oslo University Hospital Oslo Norway

Abstract

AbstractAberrant DNA methylation is a hallmark of many cancer types. Despite our knowledge of epigenetic and transcriptomic alterations in lung adenocarcinoma (LUAD), we lack robust multi‐modal molecular classifications for patient stratification. This is partly because the impact of epigenetic alterations on lung cancer development and progression is still not fully understood. To that end, we identified disease‐associated processes under epigenetic regulation in LUAD. We performed a genome‐wide expression‐methylation Quantitative Trait Loci (emQTL) analysis by integrating DNA methylation and gene expression data from 453 patients in the TCGA cohort. Using a community detection algorithm, we identified distinct communities of CpG‐gene associations with diverse biological processes. Interestingly, we identified a community linked to hormone response and lipid metabolism; the identified CpGs in this community were enriched in enhancer regions and binding regions of transcription factors such as FOXA1/2, GRHL2, HNF1B, AR, and ESR1. Furthermore, the CpGs were connected to their associated genes through chromatin interaction loops. These findings suggest that the expression of genes involved in hormone response and lipid metabolism in LUAD is epigenetically regulated through DNA methylation and enhancer‐promoter interactions. By applying consensus clustering on the integrated expression‐methylation pattern of the emQTL‐genes and CpGs linked to hormone response and lipid metabolism, we further identified subclasses of patients with distinct prognoses. This novel patient stratification was validated in an independent patient cohort of 135 patients and showed increased prognostic significance compared to previously defined molecular subtypes.

Publisher

Wiley

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3