A prognostic DNA methylation signature for stage I non-small-cell lung cancer

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 t...

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Detalles Bibliográficos
Autores: Sandoval, Juan, Méndez González, Jesús, 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 P. A., Pollán, Marina, Pajares, María José, Torre, Wenceslao, Montuenga, Luis M., Brambilla, Elisabeth, Field, John K., Roz, Luca, Lo Iacono, Marco, Scagliotti, Giorgio V., Rosell Costa, R., Beer, David G., Esteller, Manel, 1968-
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/126017
Acceso en línea:https://hdl.handle.net/2445/126017
Access Level:acceso abierto
Palabra clave:Càncer de pulmó
Metilació
ADN
Lung cancer
Methylation
DNA
Descripción
Sumario: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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