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, 08916 Badalona, Barcelona, Spain.
Barcelona Supercomputing Center (BSC-CNS), Joint BSC-CRG-IRB Research Program in Computational Biology, Carrer de Jordi Girona, 29-31, 08034 Barcelona, Spain.
Cancer Treat Res Commun. 2018;15:21-31. doi: 10.1016/j.ctarc.2018.02.003. Epub 2018 Mar 1.
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.
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).
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.
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.
本研究旨在调查种系变异作为一线铂类治疗的晚期非小细胞肺癌（NSCLC）患者预后生物标志物之间的关系。
我们对181例来自高加索地区的NSCLC患者进行了两阶段全基因组关联研究，这些患者接受了铂类化疗，随后在另外356例来自相同血统（西班牙巴伦西亚）的NSCLC患者中进行了验证。
我们确定SMYD2基因种系变异是接受化疗的晚期NSCLC患者生存的预后因素。SMYD2等位基因与总生存期缩短和疾病进展时间缩短相关。此外，富集通路分析确定40个基因中的361个变异与晚期NSCLC患者较差的预后有关。
种系SMYD2等位基因与晚期NSCLC患者一线铂类治疗的不良临床结局相关。这一结果支持了SMYD2在致癌过程中的作用，并可作为指导患者分层和治疗选择的预后标志物。
在高加索人群中进行的两阶段全基因组关联研究揭示，SMYD2基因种系遗传变异与晚期NSCLC患者一线铂类治疗中的疾病进展相关。SMYD2分析可能具有指导治疗选择的预后/预测价值，并有助于了解人类致癌过程以及化疗耐药性所涉及的通路的现有知识。
