2026-04-14T02:14:16Zhttps://recercat.cat/oai/request

oai:recercat.cat:2072/4655062025-08-31T15:58:27Zcom_2072_98col_2072_378192

00925njm 22002777a 4500 dc Ji, Xinyu author Lin, Lijuan author Fan, Juanjuan author Li, Yi author Wei, Yongyue author Shen, Sipeng author Su, Li author Shafer, Andrea author Bjaanæs, Maria Moksnes author Karlsson, Anna author Planck, Maria author Staaf, Johan author Helland, Åslaug author Esteller, M author Zhang, Ruyang author Chen, Feng author Christiani, David C author Universitat Autònoma de Barcelona author 2022 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. 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 Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC