A two‐phase epigenome‐wide four‐way gene–smoking interaction study of overall survival for early‐stage non‐small cell lung cancer

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<sub>TRIM27</sub> and cg00060500<sub>KIAA0226</sub>). 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<sub>SHISA9</sub>, 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<sub>TRIM27</sub>, cg00060500<sub>KIAA0226</sub> and g16658473<sub>SHISA9</sub>, providing novel insights into the complex mechanisms underlying NSCLC progression.

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Publication Details

Journal
Molecular Oncology
Published
2024-12-04
DOI
https://doi.org/10.1002/1878-0261.13766
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.00

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article

A two‐phase epigenome‐wide four‐way gene–smoking interaction study of overall survival for early‐stage non‐small cell lung cancer

Manel Esteller, Xiaowen Xu, Zhongwen Zhang, Maria Moksnes Bjaanæs et al.
Molecular Oncology
RNA modifications and cancer
article

A two‐phase epigenome‐wide four‐way gene–smoking interaction study of overall survival for early‐stage non‐small cell lung cancer

Manel Esteller, Xiaowen Xu, Zhongwen Zhang, Maria Moksnes Bjaanæs, Leyi Chen, Ruyang Zhang, Anna Karlsson, Maria Planck, Åslaug Helland, Johan Staaf, Feng Chen, Li Su, Liya Liu, Ning Xie, Maojie Xue, David C. Christiani, Xiang Wang, Yuqing Yang
article en

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<sub>TRIM27</sub> and cg00060500<sub>KIAA0226</sub>). 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<sub>SHISA9</sub>, 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<sub>TRIM27</sub>, cg00060500<sub>KIAA0226</sub> and g16658473<sub>SHISA9</sub>, providing novel insights into the complex mechanisms underlying NSCLC progression.

Molecular OncologyVol. 19(1)
Ningbo University (CN), Institució Catalana de Recerca i Estudis Avançats (ES), Oslo University Hospital (NO), Harvard University (US), University of Oslo (NO), Lund University (SE), China International Science and Technology Cooperation (CN), Massachusetts General Hospital (US), Josep Carreras Leukaemia Research Institute (ES), Changzhou No.2 People's Hospital (CN), Centro de Investigación Biomédica en Red de Cáncer (ES), Universitat de Barcelona (ES), Nanjing Medical University (CN)
National Natural Science Foundation of China, Government of Jiangsu Province, Ningbo University, Nanjing Medical University, Priority Academic Program Development of Jiangsu Higher Education Institutions, Qinglan Project of Jiangsu Province of China, National Institutes of Health, Natural Science Foundation of Zhejiang Province
Reduced inequalities
Openalex Percentile: Top 80%
RNA modifications and cancer
DOIOpen Access PDFOpenAlex
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