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Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients

DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation–age interaction analysis using 1,230 early-stage lung adeno...

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Autores principales: Chen, Chao, Wei, Yongyue, Wei, Liangmin, Chen, Jiajin, Chen, Xin, Dong, Xuesi, He, Jieyu, Lin, Lijuan, Zhu, Ying, Huang, Hui, You, Dongfang, Lai, Linjing, Shen, Sipeng, Duan, Weiwei, Su, Li, Shafer, Andrea, Fleischer, Thomas, Bjaanæs, Maria Moksnes, Karlsson, Anna, Planck, Maria, Wang, Rui, Staaf, Johan, Helland, Åslaug, Esteller, Manel, Zhang, Ruyang, Chen, Feng, Christiani, David C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346054/
https://www.ncbi.nlm.nih.gov/pubmed/32511103
http://dx.doi.org/10.18632/aging.103284
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author Chen, Chao
Wei, Yongyue
Wei, Liangmin
Chen, Jiajin
Chen, Xin
Dong, Xuesi
He, Jieyu
Lin, Lijuan
Zhu, Ying
Huang, Hui
You, Dongfang
Lai, Linjing
Shen, Sipeng
Duan, Weiwei
Su, Li
Shafer, Andrea
Fleischer, Thomas
Bjaanæs, Maria Moksnes
Karlsson, Anna
Planck, Maria
Wang, Rui
Staaf, Johan
Helland, Åslaug
Esteller, Manel
Zhang, Ruyang
Chen, Feng
Christiani, David C.
author_facet Chen, Chao
Wei, Yongyue
Wei, Liangmin
Chen, Jiajin
Chen, Xin
Dong, Xuesi
He, Jieyu
Lin, Lijuan
Zhu, Ying
Huang, Hui
You, Dongfang
Lai, Linjing
Shen, Sipeng
Duan, Weiwei
Su, Li
Shafer, Andrea
Fleischer, Thomas
Bjaanæs, Maria Moksnes
Karlsson, Anna
Planck, Maria
Wang, Rui
Staaf, Johan
Helland, Åslaug
Esteller, Manel
Zhang, Ruyang
Chen, Feng
Christiani, David C.
author_sort Chen, Chao
collection PubMed
description DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation–age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation–age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354(PRODH), with effects significantly modified by age (HR(interaction) = 0.989; 95% CI: 0.986–0.994; P = 9.18×10–7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HR(young) = 2.44; 95% CI: 1.26–4.72; P = 8.34×10-3; HR(elderly) = 0.58; 95% CI: 0.42–0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354(PRODH) methylation and elderly age (HR(interaction) = 0.21; 95% CI: 0.11–0.40; P = 2.20×10−6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
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spelling pubmed-73460542020-07-15 Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients Chen, Chao Wei, Yongyue Wei, Liangmin Chen, Jiajin Chen, Xin Dong, Xuesi He, Jieyu Lin, Lijuan Zhu, Ying Huang, Hui You, Dongfang Lai, Linjing Shen, Sipeng Duan, Weiwei Su, Li Shafer, Andrea Fleischer, Thomas Bjaanæs, Maria Moksnes Karlsson, Anna Planck, Maria Wang, Rui Staaf, Johan Helland, Åslaug Esteller, Manel Zhang, Ruyang Chen, Feng Christiani, David C. Aging (Albany NY) Research Paper DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation–age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation–age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354(PRODH), with effects significantly modified by age (HR(interaction) = 0.989; 95% CI: 0.986–0.994; P = 9.18×10–7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HR(young) = 2.44; 95% CI: 1.26–4.72; P = 8.34×10-3; HR(elderly) = 0.58; 95% CI: 0.42–0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354(PRODH) methylation and elderly age (HR(interaction) = 0.21; 95% CI: 0.11–0.40; P = 2.20×10−6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting. Impact Journals 2020-06-08 /pmc/articles/PMC7346054/ /pubmed/32511103 http://dx.doi.org/10.18632/aging.103284 Text en Copyright © 2020 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Chen, Chao
Wei, Yongyue
Wei, Liangmin
Chen, Jiajin
Chen, Xin
Dong, Xuesi
He, Jieyu
Lin, Lijuan
Zhu, Ying
Huang, Hui
You, Dongfang
Lai, Linjing
Shen, Sipeng
Duan, Weiwei
Su, Li
Shafer, Andrea
Fleischer, Thomas
Bjaanæs, Maria Moksnes
Karlsson, Anna
Planck, Maria
Wang, Rui
Staaf, Johan
Helland, Åslaug
Esteller, Manel
Zhang, Ruyang
Chen, Feng
Christiani, David C.
Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
title Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
title_full Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
title_fullStr Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
title_full_unstemmed Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
title_short Epigenome-wide gene–age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
title_sort epigenome-wide gene–age interaction analysis reveals reversed effects of prodh dna methylation on survival between young and elderly early-stage nsclc patients
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346054/
https://www.ncbi.nlm.nih.gov/pubmed/32511103
http://dx.doi.org/10.18632/aging.103284
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