Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC
Por:
Ji, XY, Lin, LJ, Fan, JJ, Li, Y, Wei, YY, Shen, SP, Su, L, Shafer, A, Bjaanaes, MM, Karlsson, A, Planck, M, Staaf, J, Helland, A, Esteller, M, Zhang, RY, Chen, F and Christiani, DC
Publicada:
1 feb 2022
Ahead of Print:
1 ene 2022
Resumen:
The interaction between DNA methylation of tripartite motif containing 27 (cg05293407(TRIM27)) 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 x number of years smoked) x cg05293407(TRIM27) x 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(KIAA0226) and cg17479956(EXT2). 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.
Filiaciones:
Ji, XY:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Lin, LJ:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Fan, JJ:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Li, Y:
Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
Wei, YY:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA
Nanjing Med Univ, China Int Cooperat Ctr Environm & Human Hlth, Nanjing, Peoples R China
Shen, SP:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Su, L:
Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA
Shafer, A:
Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02114 USA
Harvard Med Sch, Boston, MA 02115 USA
Bjaanaes, MM:
Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway
Karlsson, A:
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden
Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden
Planck, M:
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden
Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden
Staaf, J:
Lund Univ, Dept Clin Sci Lund, Div Oncol, Lund, Sweden
Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, Lund, Sweden
Helland, A:
Oslo Univ Hosp, Inst Canc Res, Dept Canc Genet, Oslo, Norway
Univ Oslo, Inst Clin Med, Oslo, Norway
:
Josep Carreras Leukaemia Res Inst, Barcelona, Spain
Ctr Invest Biomed Red Canc, Madrid, Spain
Inst Catalana Recerca & Estudis Avancats, Barcelona, Spain
Univ Barcelona, Sch Med & Hlth Sci, Physiol Sci Dept, Barcelona, Spain
Zhang, RY:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA
Nanjing Med Univ, China Int Cooperat Ctr Environm & Human Hlth, Nanjing, Peoples R China
Chen, F:
Nanjing Med Univ, Ctr Global Hlth, Sch Publ Hlth, Dept Biostat, SPH Bldg Room 406,101 Longmian Ave, Nanjing 211166, Jiangsu, Peoples R China
Nanjing Med Univ, China Int Cooperat Ctr Environm & Human Hlth, Nanjing, Peoples R China
Nanjing Med Univ, State Key Lab Reprod Med, Nanjing, Peoples R China
Nanjing Med Univ, Canc Ctr, Collaborat Innovat Ctr Canc Personalized Med, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Peoples R China
Christiani, DC:
Harvard TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA
Massachusetts Gen Hosp, Dept Med, Div Pulm & Crit Care, Boston, MA 02114 USA
Harvard Med Sch, Boston, MA 02115 USA
Green Published, gold
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