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

Chen, Leyi ; Wang, Xiang ; Xie, Ning ; Zhang, Zhongwen ; Xu, Xiaowen ; Xue, Maojie ; Yang, Yuqing ; Liu, Liya ; Su, Li and Bjaanæs, Maria , et al. (2025) In Molecular Oncology 19(1). p.173-187
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 (cg05293407TRIM27 and cg00060500KIAA0226). 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,... (More)

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 (cg05293407TRIM27 and cg00060500KIAA0226). 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, cg16658473SHISA9, 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, cg05293407TRIM27, cg00060500KIAA0226 and g16658473SHISA9, providing novel insights into the complex mechanisms underlying NSCLC progression.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
epigenomics, four-way interaction, gene–smoking interaction, NSCLC
in
Molecular Oncology
volume
19
issue
1
pages
15 pages
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:85211088542
  • pmid:39630602
ISSN
1574-7891
DOI
10.1002/1878-0261.13766
language
English
LU publication?
yes
id
073ad71c-cccb-4517-ac97-95a91a79b985
date added to LUP
2025-01-31 15:48:19
date last changed
2025-06-07 01:31:48
@article{073ad71c-cccb-4517-ac97-95a91a79b985,
  abstract     = {{<p>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.</p>}},
  author       = {{Chen, Leyi and Wang, Xiang and Xie, Ning and Zhang, Zhongwen and Xu, Xiaowen and Xue, Maojie and Yang, Yuqing and Liu, Liya and Su, Li and Bjaanæs, Maria and Karlsson, Anna and Planck, Maria and Staaf, Johan and Helland, Åslaug and Esteller, Manel and Christiani, David C. and Chen, Feng and Zhang, Ruyang}},
  issn         = {{1574-7891}},
  keywords     = {{epigenomics; four-way interaction; gene–smoking interaction; NSCLC}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{173--187}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Molecular Oncology}},
  title        = {{A two-phase epigenome-wide four-way gene–smoking interaction study of overall survival for early-stage non-small cell lung cancer}},
  url          = {{http://dx.doi.org/10.1002/1878-0261.13766}},
  doi          = {{10.1002/1878-0261.13766}},
  volume       = {{19}},
  year         = {{2025}},
}