TY - JOUR
T1 - Epigenetic–smoking interaction reveals histologically heterogeneous effects of TRIM27 DNA methylation on overall survival among early-stage NSCLC patients
AU - Ji, Xinyu
AU - Lin, Lijuan
AU - Shen, Sipeng
AU - Dong, Xuesi
AU - Chen, Chao
AU - Li, Yi
AU - Zhu, Ying
AU - Huang, Hui
AU - Chen, Jiajin
AU - Chen, Xin
AU - Wei, Liangmin
AU - He, Jieyu
AU - Duan, Weiwei
AU - Su, Li
AU - Jiang, Yue
AU - Fan, Juanjuan
AU - Guan, Jinxing
AU - You, Dongfang
AU - Shafer, Andrea
AU - Bjaanæs, Maria Moksnes
AU - Karlsson, Anna
AU - Planck, Maria
AU - Staaf, Johan
AU - Helland, Åslaug
AU - Esteller, Manel
AU - Wei, Yongyue
AU - Zhang, Ruyang
AU - Chen, Feng
AU - Christiani, David C.
PY - 2020/11
Y1 - 2020/11
N2 - 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.
AB - 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.
KW - DNA methylation
KW - interaction
KW - non-small-cell lung cancer
KW - overall survival
KW - prognosis
KW - TRIM27
UR - http://www.scopus.com/inward/record.url?scp=85090091990&partnerID=8YFLogxK
U2 - 10.1002/1878-0261.12785
DO - 10.1002/1878-0261.12785
M3 - Article
C2 - 33448640
AN - SCOPUS:85090091990
SN - 1574-7891
VL - 14
SP - 2759
EP - 2774
JO - Molecular Oncology
JF - Molecular Oncology
IS - 11
ER -
