Portal de investigación
A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin
Fecha de publicación:
Fecha Ahead of Print:
Autores de IIS La Fe
Participantes ajenos a IIS La Fe
- Moura, David S.
- Pena-Chilet, Maria
- Cordero Varela, Juan Antonio
- Alvarez-Alegret, Ramiro
- Agra-Pujol, Carolina
- Izquierdo, Francisco
- Ramos, Rafael
- Ortega-Medina, Luis
- Martin-Davila, Francisco
- Castilla-Ramirez, Carolina
- Nieves Hernandez-Leon, Carmen
- Romagosa, Cleofe
- Vaz Salgado, Maria Angeles
- Lavernia, Javier
- Bague, Silvia
- Mayodormo-Aranda, Empar
- Vicioso, Luis
- Hernandez Barcelo, Jose Emilio
- Rubio-Casadevall, Jordi
- de Juan, Ana
- Fiano-Valverde, Maria Concepcion
- Hindi, Nadia
- Lopez-Alvarez, Maria
- Lacerenza, Serena
- Dopazo, Joaquin
- Alvarez, Rosa
- Valverde, Claudia
- Martinez-Trufero, Javier
- Martin-Broto, Javier
Abstract
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.
Datos de la publicación
- ISSN/ISSNe:
- 1574-7891, 1878-0261
- Tipo:
- Article
- Páginas:
- 3691-3705
- Factor de Impacto:
- 1,773 SCImago ℠
- Cuartil:
- Q1 SCImago ℠
MOLECULAR ONCOLOGY ELSEVIER SCI LTD
Citas Recibidas en Web of Science: 7
Documentos
- No hay documentos
Filiaciones
Keywords
- gene signature, predictive biomarkers, trabectedin
Campos de estudio
Proyectos asociados
ESTUDIO POSAUTORIZACIÓN OBSERVACIONAL EUROPEO PARA EVALUAR LA UTILIZACIÓN Y LA SEGURIDAD DEL CITRATO DE CAFEÍNA (PEYONA®) EN EL TRATAMIENTO DE NEONATOS PREMATUROS.
Investigador Principal: PILAR SÁENZ GONZÁLEZ
CHI-CAF-2011-01 . 2012
ENSAYO CLINICO, MULTICENTRICO, CONTROLADO, ALEATORIZADO, ENMASCARADO PARA COMPARAR LA SEGURIDAD Y LA EFECTIVIDAD DE SURFAXIN (LUCINANTANT) FRENTE A CUROSURF EN LA PREVENCION Y TRATAMIENTO DEL SINDROME DE DISTRES RESPIRATORIO (SDR) EN NEONATOS PREMATUROS.
Investigador Principal: JOSE MANUEL ROQUES SERRADILLA
KL4-IRDS-02
ESTUDIO DE LOS FACTORES DE RIESGO ASOCIADOS A LAS EXTUBACIONES ACCIDENTALES
Investigador Principal: MARTA AGUAR CARRASCOSA
ACCEX
Cita
Moura DS,Pena M,Cordero JA,Alvarez R,Agra C,Izquierdo F,Ramos R,Ortega L,Martin F,Castilla C,Nieves Hernandez C,Romagosa C,Vaz MA,Lavernia J,Bague S,Mayodormo E,Vicioso L,Hernandez JE,Rubio J,de Juan A,Fiano MC,Hindi N,Lopez M,Lacerenza S,Dopazo J,Gutierrez A,Alvarez R,Valverde C,Martinez J,Martin J. A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin. Mol Oncol. 2021. 15. (12):p. 3691-3705. IF:7,449. (1).