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Title: A prognostic DNA methylation signature for stage I non-small-cell lung cancer
Author: Sandoval, Juan
Méndez González, Jesus
Nadal, Ernest
Chen, Guoan
Carmona, F. Javier
Sayols, Sergi
Moran, Sebastian
Heyn, Holger
Vizoso, Miguel
Gómez, Antonio
Sánchez Céspedes, Montserrat
Assenov, Yassen
Müller, Fabian
Bock, Christoph
Taron, Miquel
Mora, Josefina
Muscarella, Lucia A.
Liloglou, Triantafillos
Davies, Michael
Pollán, Marina
Pajares, Maria J
Torre, Wenceslao
Montuenga, Luis M.
Brambill, Elisabeth
Field, John K
Roz, Luca
Lo Iacono, Marco
Scagliotti, Giorgio V.
Rosell, Rafael
Beer, David G.
Esteller, Manel
Keywords: Càncer de pulmó
Lung cancer
Issue Date: 10-Nov-2013
Publisher: American Society of Clinical Oncology
Abstract: Purpose Non-small-cell lung cancer (NSCLC) is a tumor in which only small improvements in clinical outcome have been achieved. The issue is critical for stage I patients for whom there are no available biomarkers that indicate which high-risk patients should receive adjuvant chemotherapy. We aimed to find DNA methylation markers that could be helpful in this regard. Patients and Methods A DNA methylation microarray that analyzes 450,000 CpG sites was used to study tumoral DNA obtained from 444 patients with NSCLC that included 237 stage I tumors. The prognostic DNA methylation markers were validated by a single-methylation pyrosequencing assay in an independent cohort of 143 patients with stage I NSCLC. Results Unsupervised clustering of the 10,000 most variable DNA methylation sites in the discovery cohort identified patients with high-risk stage I NSCLC who had shorter relapse-free survival (RFS; hazard ratio [HR], 2.35; 95% CI, 1.29 to 4.28; P = .004). The study in the validation cohort of the significant methylated sites from the discovery cohort found that hypermethylation of five genes was significantly associated with shorter RFS in stage I NSCLC: HIST1H4F, PCDHGB6, NPBWR1, ALX1, and HOXA9. A signature based on the number of hypermethylated events distinguished patients with high-and low-risk stage I NSCLC (HR, 3.24; 95% CI, 1.61 to 6.54; P = .001). Conclusion The DNA methylation signature of NSCLC affects the outcome of stage I patients, and it can be practically determined by user-friendly polymerase chain reaction assays. The analysis of the best DNA methylation biomarkers improved prognostic accuracy beyond standard staging. (C) 2013 by American Society of Clinical Oncology.
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It is part of: Journal of Clinical Oncology, 2013, vol. 31, num. 32, p. 4140-4147
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ISSN: 0732-183X
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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