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 (Nanjing Medical University)
Lin, Lijuan (Nanjing Medical University)
Fan, Juanjuan (Nanjing Medical University)
Li, Yi (University of Michigan)
Wei, Yongyue (Nanjing Medical University)
Shen, Sipeng (Nanjing Medical University)
Su, Li (Harvard T.H. Chan School of Public Health (Estats Units d'Amèrica))
Shafer, Andrea (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. Hospital Universitari Germans Trias i Pujol)
Zhang, Ruyang (Nanjing Medical University)
Chen, Feng (Nanjing Medical University)
Christiani, David C (Harvard Medical School)
Universitat Autònoma de Barcelona

Fecha:	2022
Resumen:	The interaction between DNA methylation of tripartite motif containing 27 (cg05293407) 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 × 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 and cg17479956. 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.
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Carcinoma, Non-Small-Cell Lung ; CpG Islands ; DNA Methylation ; DNA-Binding Proteins ; Epigenesis, Genetic ; Epigenome ; Genome-Wide Association Study ; Humans ; Lung Neoplasms ; Nuclear Proteins ; Smoking
Publicado en:	Molecular Oncology, Vol. 16 Núm. 3 (february 2022) , p. 717-731, ISSN 1878-0261

DOI: 10.1002/1878-0261.13167
PMID: 34932879

15 p, 2.0 MB

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