학술논문
Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early‐stage NSCLC patients
Document Type
article
Author
Xinyu Ji; Lijuan Lin; Sipeng Shen; Xuesi Dong; Chao Chen; Yi Li; Ying Zhu; Hui Huang; Jiajin Chen; Xin Chen; Liangmin Wei; Jieyu He; Weiwei Duan; Li Su; Yue Jiang; Juanjuan Fan; Jinxing Guan; Dongfang You; Andrea Shafer; Maria Moksnes Bjaanæs; Anna Karlsson; Maria Planck; Johan Staaf; Åslaug Helland; Manel Esteller; Yongyue Wei; Ruyang Zhang; Feng Chen; David C. Christiani
Source
Molecular Oncology, Vol 14, Iss 11, Pp 2759-2774 (2020)
Subject
Language
English
ISSN
1878-0261
1574-7891
1574-7891
Abstract
Tripartite motif containing 27 (TRIM27) is highly expressed in lung cancer, including non‐small‐cell lung cancer (NSCLC). Here, we profiled DNA methylation of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) tumours from 613 early‐stage NSCLC patients and evaluated associations between CpG methylation of TRIM27 and overall survival. Significant CpG probes were confirmed in 617 samples from The Cancer Genome Atlas. The methylation of the CpG probe cg05293407TRIM27 was significantly associated with overall survival in patients with LUSC (HR = 1.65, 95% CI: 1.30–2.09, P = 4.52 × 10−5), but not in patients with LUAD (HR = 1.08, 95% CI: 0.87–1.33, P = 0.493). As incidence of LUSC is associated with higher smoking intensity compared to LUAD, we investigated whether smoking intensity impacted on the prognostic effect of cg05293407TRIM27 methylation in NSCLC. LUSC patients had a higher average pack‐year of smoking (37.49LUAD vs 54.79LUSC, P = 1.03 × 10−19) and included a higher proportion of current smokers than LUAD patients (28.24%LUAD vs 34.09%LUSC, P = 0.037). cg05293407TRIM27 was significantly associated with overall survival only in NSCLC patients with medium–high pack‐year of smoking (HR = 1.58, 95% CI: 1.26–1.96, P = 5.25 × 10−5). We conclude that cg05293407TRIM27 methylation is a potential predictor of LUSC prognosis, and smoking intensity may impact on its prognostic value across the various types of NSCLC.