Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/178917
Title: Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
Author: Chen, Chao
Wei, Yongyue
Wei, Liangmin
Chen, Jiajin
Chen, Xin
Dong, Xuesi
He, Jieyu
Lin, Lijuan
Zhu, Ying
Huang, Hui
You, Donfang
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.
Keywords: Envelliment
Metilació
Càncer de pulmó
Aging
Methylation
Lung cancer
Issue Date: 8-Jun-2020
Publisher: Impact Journals
Abstract: 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, cg14326354PRODH, with effects significantly modified by age (HRinteraction = 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 (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67×10-3). Moreover, there was an antagonistic interaction between low cg14326354PRODH methylation and elderly age (HRinteraction = 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.
Note: Reproducció del document publicat a: https://doi.org/10.18632/aging.103284
It is part of: Aging, 2020, vol. 12, num. 11, p. 10642-10662
URI: http://hdl.handle.net/2445/178917
Related resource: https://doi.org/10.18632/aging.103284
ISSN: 1945-4589
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)

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