A two-phase epigenome-wide four-way gene-smoking interaction study of overall survival for early-stage non-small cell lung cancer
Chen, Leyi (Nanjing Medical University)
Wang, Xiang (Nanjing Medical University)
Xie, Ning (Nanjing Medical University)
Zhang, Zhongwen (Nanjing Medical University)
Xu, Xiaowen (Nanjing Medical University)
Xue, Maojie (Nanjing Medical University)
Yang, Yuqing (Nanjing Medical University)
Liu, Liya (Ningbo University)
Su, Li (Harvard Medical School)
Bjaanæs, Maria Moksnes (Oslo University Hospital (Oslo, Noruega))
Karlsson, Anna (Lund University)
Planck, Maria (Lund University)
Staaf, Johan (Lund University)
Helland, Åslaug (University of Oslo)
Esteller, M (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Christiani, David C. (Harvard Medical School)
Chen, Feng (Nanjing Medical University)
Zhang, Ruyang (Nanjing Medical University)

Date:	2025
Abstract:	High-order interactions associated with non-small cell lung cancer (NSCLC) survival may elucidate underlying molecular mechanisms and identify potential therapeutic targets. Our previous work has identified a three-way interaction among pack-year of smoking (the number of packs of cigarettes smoked per day multiplied by the number of years the person has smoked) and two DNA methylation probes (cg05293407 and cg00060500). However, whether a four-way interaction exists remains unclear. Therefore, we adopted a two-phase design to identify the four-way gene-smoking interactions by a hill-climbing strategy on the basis of the previously detected three-way interaction. One CpG probe, cg16658473, was identified with FDR-q ≤ 0. 05 in the discovery phase and P ≤ 0. 05 in the validation phase. Meanwhile, the four-way interaction improved the discrimination ability for the prognostic prediction model, as indicated by the area under the receiver operating characteristic curve (AUC) for both 3- and 5-year survival. In summary, we identified a four-way interaction associated with NSCLC survival among pack-year of smoking, cg05293407, cg00060500 and g16658473, providing novel insights into the complex mechanisms underlying NSCLC progression.
Note:	Altres ajuts: This study was supported by the National Natural Science Foundation of China (82220108002 to FC and 82273737 to RZ), the US National Institutes of Health (CA209414, CA249096, CA092824, and ES000002 to DCC), Zhejiang Provincial Natural Science Foundation of China (ZCLY24H2601 to LL)
Rights:	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.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Epigenomics ; Four-way interaction ; Gene-smoking interaction ; NSCLC
Published in:	Molecular oncology, Vol. 19 Núm. 1 (January 2025) , p. 173-187, ISSN 1878-0261

DOI: 10.1002/1878-0261.13766
PMID: 39630602

15 p, 1.1 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles