Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC
(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.
(Less)
- author
- organization
- publishing date
- 2022-02
- 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
- 2024-09-28 01:40:23
@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}}, }