Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
Chen, C. (China International Cooperation Center for Environment and Human Health. Nanjing Medical University)
Wei, Y. (Department of Environmental Health. Harvard T.H. Chan School of Public Health)
Wei, Liangmin (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
Chen, J. (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
Chen, X. (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
Dong, X. (Department of Epidemiology and Biostatistics. School of Public Health. Southeast University)
He, J. (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
Lin, L. (Department of Environmental Health. Harvard T.H. Chan School of Public Health)
Zhu, Y. (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
Huang, H. (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
You, D. (Department of Environmental Health. Harvard T.H. Chan School of Public Health)
Lai, L. (Department of Biostatistics. Center for Global Health. School of Public Health. Nanjing Medical University)
Shen, S. (Department of Environmental Health. Harvard T.H. Chan School of Public Health)
Duan, W. (Department of Bioinformatics. School of Biomedical Engineering and Informatics. Nanjing Medical University)
Su, L. (Department of Environmental Health. Harvard T.H. Chan School of Public Health)
Shafer, A. (Harvard Medical School)
Fleischer, T. (Department of Cancer Genetics. Institute for Cancer Research. Oslo University Hospital)
Bjaanæs, Maria Moksnes (Department of Cancer Genetics. Institute for Cancer Research. Oslo University Hospital)
Karlsson, A. (Division of Oncology and Pathology. Department of Clinical Sciences Lund and CREATE Health Strategic Center for Translational Cancer Research. Lund University)
Planck, M. (Division of Oncology and Pathology. Department of Clinical Sciences Lund and CREATE Health Strategic Center for Translational Cancer Research. Lund University)
Wang, R. (Department of Medical Oncology. Jinling Hospital. School of Medicine. Nanjing University)
Staaf, J. (Division of Oncology and Pathology. Department of Clinical Sciences Lund and CREATE Health Strategic Center for Translational Cancer Research. Lund University)
Helland, Å. (Institute of Clinical Medicine. University of Oslo)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Zhang, R. (Department of Medical Oncology. Jinling Hospital. School of Medicine. Nanjing University)
Chen, F. (Jiangsu Key Lab of Cancer Biomarkers. Prevention and Treatment. Cancer Center. Collaborative Innovation Center for Cancer Personalized Medicine. Nanjing Medical University)
Christiani, David C (Harvard Medical School)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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, with effects significantly modified by age (HR = 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 = 2. 44; 95% CI: 1. 26-4. 72; P = 8. 34×10-3; HR = 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 = 0. 21; 95% CI: 0. 11-0. 40; P = 2. 20×10-6). In summary, low methylation of cg14326354 might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Overall survival ; DNA methylation ; Methylation-age interaction analysis ; Non-small cell lung cancer ; Aging
Publicat a:	Aging (Albany NY), Vol. 12 Núm. 11 (15 2020) , p. 10642-10662, ISSN 1945-4589

DOI: 10.18632/aging.103284
PMID: 32511103

21 p, 2.7 MB

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