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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

Chen, Chao ; Wei, Yongyue ; Wei, Liangmin ; Chen, Jiajin ; Chen, Xin ; Dong, Xuesi ; He, Jieyu ; Lin, Lijuan ; Zhu, Ying and Huang, Hui , et al. (2020) In Aging 12(11). p.10642-10662
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... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
Aging, DNA methylation, Methylation-age interaction analysis, Non-small cell lung cancer, Overall survival
in
Aging
volume
12
issue
11
pages
21 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85087094490
  • pmid:32511103
ISSN
1945-4589
DOI
10.18632/aging.103284
language
English
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yes
id
3e74ad5b-c398-4ceb-af62-8f1d9ee8414b
date added to LUP
2020-07-08 09:28:19
date last changed
2020-07-16 03:51:55
@article{3e74ad5b-c398-4ceb-af62-8f1d9ee8414b,
  abstract     = {<p>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<sub>PRODH</sub>, with effects significantly modified by age (HR<sub>interaction</sub> = 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<sub>young</sub> = 2.44; 95% CI: 1.26-4.72; P = 8.34×10-3; HR<sub>elderly</sub> = 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 (HR<sub>interaction</sub> = 0.21; 95% CI: 0.11-0.40; P = 2.20×10-6). In summary, low methylation of cg14326354<sub>PRODH</sub> might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.</p>},
  author       = {Chen, Chao and Wei, Yongyue and Wei, Liangmin and Chen, Jiajin and Chen, Xin and Dong, Xuesi and He, Jieyu and Lin, Lijuan and Zhu, Ying and Huang, Hui and You, Dongfang and Lai, Linjing and Shen, Sipeng and Duan, Weiwei and Su, Li and Shafer, Andrea and Fleischer, Thomas and Bjaanæs, Maria Moksnes and Karlsson, Anna and Planck, Maria and Wang, Rui and Staaf, Johan and Helland, Åslaug and Esteller, Manel and Zhang, Ruyang and Chen, Feng and Christiani, David C.},
  issn         = {1945-4589},
  language     = {eng},
  number       = {11},
  pages        = {10642--10662},
  publisher    = {Impact Journals, LLC},
  series       = {Aging},
  title        = {Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients},
  url          = {http://dx.doi.org/10.18632/aging.103284},
  doi          = {10.18632/aging.103284},
  volume       = {12},
  year         = {2020},
}