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Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC

Ji, Xinyu ; Lin, Lijuan ; Fan, Juanjuan ; Li, Yi ; Wei, Yongyue ; Shen, Sipeng ; Su, Li ; Shafer, Andrea ; Bjaanæs, Maria Moksnes and Karlsson, Anna LU , et al. (2022) In Molecular Oncology 16(3). p.717-731
Abstract

The interaction between DNA methylation of tripartite motif containing 27 (cg05293407TRIM27) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early-stage non-small-cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three-way interactions. A two-phase study was adopted to identify three-way interactions in the form of pack-year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407TRIM27 × epigenome-wide DNA methylation CpG probe. Two CpG probes were identified with FDR-q ≤ 0.05 in the discovery phase and P ≤ 0.05 in the validation phase:... (More)

The interaction between DNA methylation of tripartite motif containing 27 (cg05293407TRIM27) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early-stage non-small-cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three-way interactions. A two-phase study was adopted to identify three-way interactions in the form of pack-year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407TRIM27 × epigenome-wide DNA methylation CpG probe. Two CpG probes were identified with FDR-q ≤ 0.05 in the discovery phase and P ≤ 0.05 in the validation phase: cg00060500KIAA0226 and cg17479956EXT2. Compared to a prediction model with only clinical information, the model added 42 significant three-way interactions using a looser criterion (discovery: FDR-q ≤ 0.10, validation: P ≤ 0.05) had substantially improved the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model for both 3-year and 5-year survival. Our research identified the complex interaction effects among multiple environment and epigenetic factors, and provided therapeutic target for NSCLC patients.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Molecular Oncology
volume
16
issue
3
pages
15 pages
publisher
Elsevier
external identifiers
  • pmid:34932879
  • scopus:85122621458
ISSN
1574-7891
DOI
10.1002/1878-0261.13167
language
English
LU publication?
yes
id
52602e54-76b4-4fa8-8dc3-f06fe35f02d2
date added to LUP
2022-03-07 11:41:58
date last changed
2022-07-28 07:23:27
@article{52602e54-76b4-4fa8-8dc3-f06fe35f02d2,
  abstract     = {{<p>The interaction between DNA methylation of tripartite motif containing 27 (cg05293407<sub>TRIM27</sub>) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early-stage non-small-cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three-way interactions. A two-phase study was adopted to identify three-way interactions in the form of pack-year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407<sub>TRIM27</sub> × epigenome-wide DNA methylation CpG probe. Two CpG probes were identified with FDR-q ≤ 0.05 in the discovery phase and P ≤ 0.05 in the validation phase: cg00060500<sub>KIAA0226</sub> and cg17479956<sub>EXT2</sub>. Compared to a prediction model with only clinical information, the model added 42 significant three-way interactions using a looser criterion (discovery: FDR-q ≤ 0.10, validation: P ≤ 0.05) had substantially improved the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model for both 3-year and 5-year survival. Our research identified the complex interaction effects among multiple environment and epigenetic factors, and provided therapeutic target for NSCLC patients.</p>}},
  author       = {{Ji, Xinyu and Lin, Lijuan and Fan, Juanjuan and Li, Yi and Wei, Yongyue and Shen, Sipeng and Su, Li and Shafer, Andrea and Bjaanæs, Maria Moksnes and Karlsson, Anna and Planck, Maria and Staaf, Johan and Helland, Åslaug and Esteller, Manel and Zhang, Ruyang and Chen, Feng and Christiani, David C.}},
  issn         = {{1574-7891}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{717--731}},
  publisher    = {{Elsevier}},
  series       = {{Molecular Oncology}},
  title        = {{Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC}},
  url          = {{http://dx.doi.org/10.1002/1878-0261.13167}},
  doi          = {{10.1002/1878-0261.13167}},
  volume       = {{16}},
  year         = {{2022}},
}