Early-stage lung adenocarcinoma affects DNA methylation and gene expression in adjacent tissues

The impact of early-stage tumors on gene expression in adjacent tissues remains uncertain, despite the known influence of the tumor microenvironment on tumor progression. Here, we systematically analyze early-stage lung adenocarcinoma (LUAD) and surrounding tissues across multiple distinct regions, from the tumor core to distant tissues. DNA methylation profiling in a 12-patient cohort reveals two distinct patterns of methylation changes. Steep changes occurring at the tumor boundary and shallow changes showing a gradual shift over increasing distance to the tumor. Approximately 17,000 CpG sites demonstrate shallow changing trends without clear boundaries, potentially affecting 2655 genes. In half of the patients, tissues within 10 mm beyond the tumor show methylation patterns similar to tumors. We test mRNA expression of key genes affected by these methylation patterns and observe that the protein expression pattern of WNT7B demonstrates no steep changes at the tumor boundary, supporting their regulatory role. Adding a 59-patient four-year-prognosis cohort allowed us to rigorously assess the clinical relevance of these methylation change trends. These shallow changes reflect tumor characteristics and have the potential for prognostic prediction in patients, warranting further investigation.

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Publication Details

Journal
EMBO Reports
Published
2025-11-03
DOI
https://doi.org/10.1038/s44319-025-00612-4
Primary Topic
Epigenetics and DNA Methylation
Type
article
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article

Early-stage lung adenocarcinoma affects DNA methylation and gene expression in adjacent tissues

Yifan Wu, Zhicheng Huang, Jian‐Qun Chen, Daoyun Wang et al.
EMBO Reports
Epigenetics and DNA Methylation
article

Early-stage lung adenocarcinoma affects DNA methylation and gene expression in adjacent tissues

Yifan Wu, Zhicheng Huang, Jian‐Qun Chen, Daoyun Wang, Jianchao Xue, Qihan Chen, Liucun Zhu, Xiaoyi Zheng, Haoxiang Xu, Chenzheng Guan, Ji Li, Qiang Wang, Bowen Li, Yadong Wang, Shanqing Li, Naixin Liang, Sainan Wang, Zichen Jiao, David J. Kerr, Yao Tang, Lan Song, Ka Luk Fung
article en

Abstract

The impact of early-stage tumors on gene expression in adjacent tissues remains uncertain, despite the known influence of the tumor microenvironment on tumor progression. Here, we systematically analyze early-stage lung adenocarcinoma (LUAD) and surrounding tissues across multiple distinct regions, from the tumor core to distant tissues. DNA methylation profiling in a 12-patient cohort reveals two distinct patterns of methylation changes. Steep changes occurring at the tumor boundary and shallow changes showing a gradual shift over increasing distance to the tumor. Approximately 17,000 CpG sites demonstrate shallow changing trends without clear boundaries, potentially affecting 2655 genes. In half of the patients, tissues within 10 mm beyond the tumor show methylation patterns similar to tumors. We test mRNA expression of key genes affected by these methylation patterns and observe that the protein expression pattern of WNT7B demonstrates no steep changes at the tumor boundary, supporting their regulatory role. Adding a 59-patient four-year-prognosis cohort allowed us to rigorously assess the clinical relevance of these methylation change trends. These shallow changes reflect tumor characteristics and have the potential for prognostic prediction in patients, warranting further investigation.

EMBO ReportsVol. 26(23)
Shanghai University (CN), Shanghai University of Engineering Science (CN), China Pharmaceutical University (CN), University of Toronto (CA), Chinese Academy of Medical Sciences & Peking Union Medical College (CN), University of Macau (MO), Peking Union Medical College Hospital (CN), John Radcliffe Hospital (GB), University of Bristol (GB), University of Oxford (GB), Nanjing Drum Tower Hospital (CN), Nanjing University (CN)
Openalex Percentile: Top 71%
Epigenetics and DNA Methylation
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