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

Aging
Chao ChenDavid C Christiani

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...Continue Reading

References

May 12, 2000·The Journal of Biological Chemistry·A M Cuervo, J F Dice
May 25, 2007·Nature·Adrian Bird
Jun 1, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Rebecca Suk HeistDavid C Christiani
Jun 15, 2007·Trends in Genetics : TIG·Mario F Fraga, Manel Esteller
Jul 31, 2007·Cell·Manuel ColladoManuel Serrano
Oct 9, 2007·Proceedings of the National Academy of Sciences of the United States of America·Zhaohui FengArnold J Levine
May 10, 2008·Bioinformatics·Pan DuSimon M Lin
May 2, 2009·Journal of Clinical Immunology·Antero Salminen, Kai Kaarniranta
Dec 21, 2010·Oncogene·M M ChaturvediB B Aggarwal
Feb 18, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ravi K AmaravadiEileen White
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Jun 19, 2012·Clinical Epigenetics·Liang LiuTrygve O Tollefsbol
Aug 14, 2012·BioFactors·Wei Liu, James M Phang
Jan 15, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Yi-an ChenRosanna Weksberg
Feb 21, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Francesco MarabitaDavid Gomez-Cabrero
May 10, 2013·Frontiers in Genetics·Harold T BaeThomas T Perls
Jun 28, 2013·Nature·Jessica Wright
Aug 14, 2013·Nature Communications·Jong-Ok PyoYong-Keun Jung
Oct 2, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Juan SandovalManel Esteller
Nov 16, 2013·The Journal of Clinical Investigation·Abdul M MondalCurtis C Harris
Oct 4, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Anna KarlssonJohan Staaf
Jan 17, 2015·Nature·Dirk Schübeler
Jul 29, 2015·Human Genomics·Marco TrerotolaSaverio Alberti
Apr 23, 2016·Epigenomics·Shijie C ZhengAndrew E Teschendorff
Jun 3, 2016·CA: a Cancer Journal for Clinicians·Kimberly D MillerAhmedin Jemal
Sep 16, 2016·Nature Reviews. Genetics·Peter A JonesStephen Baylin
Jan 13, 2017·Nature·Nadja S KathederTor Erik Rusten
Dec 9, 2017·Frontiers in Oncology·Markus SchossererMichael Breitenbach
Dec 21, 2017·Nature·Maja MilanovicClemens A Schmitt
Apr 6, 2018·Clinical Epigenetics·Yongyue WeiDavid C Christiani
Jan 9, 2019·CA: a Cancer Journal for Clinicians·Rebecca L SiegelAhmedin Jemal

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Software Mentioned

R package minfi
R
R package clusterProfiler
Genome Studio
R package lumi
R package sva
R package survival

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