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Genomic profiling in advanced stage non-small-cell lung cancer patients with platinum-based chemotherapy identifies germline variants with prognostic value in SMYD2

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Cancer Treatment and Research Communications 2018年 15卷 21-31页

作者： Galván-Femenía, Iván Guindo, Marta Duran, Xavier Calabuig-Fariñas, Sílvia Mercader, Josep Maria Ramirez, Jose Luis Rosell, Rafael Torrents, David Carreras, Anna Kohno, Takashi Jantus-Lewintre, Eloisa Camps, Carlos Perucho, Manuel Sumoy, Lauro Yokota, Jun de Cid, Rafael Genomes For life-GCAT Lab. Program of Predictive and Personalized Medicine of Cancer (PMPPC) Institute for Health Science Research Germans Trias i Pujol (IGTP) Can Ruti Biomedical Campus Crta de Can Ruti Camí de les Escoles S/N Badalona 08916 Barcelona Spain Barcelona Supercomputing Center (BSC-CNS) Joint BSC-CRG-IRB Research Program in Computational Biology Carrer de Jordi Girona 29-31 Barcelona 08034 Spain Department of Medical Oncology Hospital General Universitario de Valencia Avenida Tres Cruces 2 València 46014 Spain Molecular Oncology Laboratory Fundación Hospital General Universitario de Valencia Avda. Tres Cruces s/n València 46014 Spain Department of Pathology Universitat de València Av. de Blasco Ibáñez 13 València 46010 Spain Program of Predictive and Personalized Medicine of Cancer (PMPPC) Institute for Health Science Research Germans Trias i Pujol (IGTP) Can Ruti Biomedical Campus Crta de Can Ruti Camí de les Escoles S/N Badalona 08916 Barcelona Spain ICREA Catalan Institution for Research and Advanced Studies Spain Division of Genome Biology National Cancer Center Research Institute 5-1-1 Tsukiji Chuo-ku Tokyo 104-0045 Japan Molecular Oncology Laboratory Fundación Hospital General Universitario de València Avda. Tres Cruces s/n València 46014 Spain Department of Biotechnology Universitat Politècnica de València Camí de Vera s/n València 46022 Spain Department of Medicine Universitat de València Av. de Blasco Ibáñez 13 València 46010 Spain Genomics and Bioinformatics. Program of Predictive and Personalized Medicine of Cancer (PMPPC) Institute for Health Science Research Germans Trias i Pujol (IGTP) Can Ruti Biomedical Campus Crta de Can Ruti Camí de les Escoles S/N Badalona 08916 Barcelona Spain Programs in Metabolism and Medical & Population Genetics Broad Institute of Harvard and MIT Cambridge Massachusetts United States Diabetes Unit and Center for Human Genetic Research Massachusetts General Hospital Boston Massachuse

Objective: The aim of the study was to investigate the relationship between germline variations as a prognosis biomarker in patients with advanced Non-Small-Cell-Lung-Cancer (NSCLC) subjected to first-line platinum-based treatment. Materials and Methods: We carried out a two-stage genome-wide-association study in non-small-cell lung cancer patients with platinum-based chemotherapy in an exploratory sample of 181 NSCLC patients from Caucasian origin, followed by a validation on 356 NSCLC patients from the same ancestry (Valencia, Spain). Results: We identified germline variants in SMYD2 as a prognostic factor for survival in patients with advanced NSCLC receiving chemotherapy. SMYD2 alleles are associated to a decreased overall survival and with a reduced Time to Progression. In addition, enrichment pathway analysis identified 361 variants in 40 genes to be involved in poorer outcome in advanced-stage NSCLC patients. Conclusion: Germline SMYD2 alleles are associated with bad clinical outcome of first-line platinum-based treatment in advanced NSCLC patients. This result supports the role of SMYD2 in the carcinogenic process, and might be used as prognostic signature directing patient stratification and the choice of therapy. A two-Stage Genome wide association study in Caucasian population reveals germline genetic variation in SMYD2 associated to progression disease in first-line platinum-based treatment in advanced NSCLC patients. SMYD2 profiling might have prognostic / predictive value directing choice of therapy and enlighten current knowledge on pathways involved in human carcinogenesis as well in resistance to chemotherapy. © 2018 The Authors

关键词： Advanced stage Genome-Wide-Association Studies Lung cancer NSCLC Prognostic factors

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