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oai:recercat.cat:2445/1260172025-12-05T09:35:05Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917

A prognostic DNA methylation signature for stage I non-small-cell lung cancer 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 Càncer de pulmó Metilació ADN Lung cancer Methylation DNA 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. 2018-11-12T12:24:15Z 2018-11-12T12:24:15Z 2013-11-10 2018-11-12T12:24:15Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 0732-183X https://hdl.handle.net/2445/126017 662772 eng Reproducció del document publicat a: https://doi.org/10.1200/JCO.2012.48.5516 Journal of Clinical Oncology, 2013, vol. 31, num. 32, p. 4140-4147 https://doi.org/10.1200/JCO.2012.48.5516 info:eu-repo/grantAgreement/EC/FP7/258677/EU//CURELUNG (c) American Society of Clinical Oncology, 2013 info:eu-repo/semantics/openAccess 8 p. application/pdf American Society of Clinical Oncology Articles publicats en revistes (Ciències Fisiològiques)