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

Research output: Contribution to journalArticle


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.


  • Chao Chen
  • Yongyue Wei
  • Liangmin Wei
  • Jiajin Chen
  • Xin Chen
  • Xuesi Dong
  • Jieyu He
  • Lijuan Lin
  • Ying Zhu
  • Hui Huang
  • Dongfang You
  • Linjing Lai
  • Sipeng Shen
  • Weiwei Duan
  • Li Su
  • Andrea Shafer
  • Thomas Fleischer
  • Maria Moksnes Bjaanæs
  • Rui Wang
  • Åslaug Helland
  • Manel Esteller
  • Ruyang Zhang
  • Feng Chen
  • David C. Christiani
External organisations
  • Nanjing Medical University
  • Massachusetts General Hospital
  • Oslo university hospital
  • Nanjing University
  • University of Oslo
  • Catalan Institution for Research and Advanced Studies
  • University of Barcelona
  • Southeast University
  • Jinling Hospital, Nanjing
  • Josep Carreras Leukaemia Research Institute (IJC)
  • CIBERONC Centro de Investigación Biomédica en Red Cáncer
  • Harvard University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • Aging, DNA methylation, Methylation-age interaction analysis, Non-small cell lung cancer, Overall survival
Original languageEnglish
Pages (from-to)10642-10662
Number of pages21
Issue number11
Publication statusPublished - 2020
Publication categoryResearch