A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin

Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively....

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Autores: Moura, David S., Peña-Chilet, María|||0000-0002-6445-9617, Cordero Varela, Juan Antonio|||0000-0002-7373-5433, Alvarez-Alegret, Ramiro, Agra Pujol, Carolina|||0000-0003-4843-5786, Izquierdo, Francisco, Ramos, Rafel|||0000-0001-7970-5537, Ortega-Medina, Luis, Martin-Davila, Francisco, Castilla-Ramirez, Carolina, Hernandez-Leon, Carmen Nieves, Romagosa Perez Portabella, Maria Cleofe|||0000-0002-9478-7320, Vaz Salgado, María Ángeles, Lavernia, Javier, Bagué Rosell, Sílvia|||0000-0001-9980-7231, Mayodormo-Aranda, Empar, Vicioso, Luis, Hernández Barceló, José Emilio, Rubio-Casadevall, Jordi|||0000-0002-3516-6970, de Juan Ferre, Ana|||0000-0002-5852-9068, Fiaño-Valverde, María Concepción, Hindi, Nadia|||0000-0002-5864-762X, Lopez-Alvarez, María, Lacerenza, Serena, Dopazo, Joaquín|||0000-0003-3318-120X, Gutiérrez, Antonio|||0000-0001-9062-077X, Alvarez, Rosa|||0000-0003-0935-8298, Valverde Morales, Claudia Maria, Martínez Trufero, Javier|||0000-0002-0997-2573, Martín-Broto, Javier|||0000-0001-7350-6916
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:270211
Acceso en línea:https://ddd.uab.cat/record/270211
https://dx.doi.org/urn:doi:10.1002/1878-0261.12996
Access Level:acceso abierto
Palabra clave:Gene signature
Predictive biomarkers
Trabectedin
Descripción
Sumario:Predictive biomarkers of trabectedin represent an unmet need in advanced soft-tissue sarcomas (STS). DNA damage repair (DDR) genes, involved in homologous recombination or nucleotide excision repair, had been previously described as biomarkers of trabectedin resistance or sensitivity, respectively. The majority of these studies only focused on specific factors (ERCC1, ERCC5, and BRCA1) and did not evaluate several other DDR-related genes that could have a relevant role for trabectedin efficacy. In this retrospective translational study, 118 genes involved in DDR were evaluated to determine, by transcriptomics, a predictive gene signature of trabectedin efficacy. A six-gene predictive signature of trabectedin efficacy was built in a series of 139 tumor samples from patients with advanced STS. Patients in the high-risk gene signature group showed a significantly worse progression-free survival compared with patients in the low-risk group (2.1 vs 6.0 months, respectively). Differential gene expression analysis defined new potential predictive biomarkers of trabectedin sensitivity (PARP3 and CCNH) or resistance (DNAJB11 and PARP1). Our study identified a new gene signature that significantly predicts patients with higher probability to respond to treatment with trabectedin. Targeting some genes of this signature emerges as a potential strategy to enhance trabectedin efficacy.

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