RT Journal Article
T1 A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin.
A1 Moura, David S
A1 Peña-Chilet, Maria
A1 Cordero-Varela, Juan Antonio
A1 Alvarez-Alegret, Ramiro
A1 Agra-Pujol, Carolina
A1 Izquierdo, Francisco
A1 Ramos, Rafael
A1 Ortega-Medina, Luis
A1 Martin-Davila, Francisco
A1 Castilla-Ramirez, Carolina
A1 Hernandez-Leon, Carmen Nieves
A1 Romagosa, Cleofe
A1 Vaz-Salgado, Maria Angeles
A1 Lavernia, Javier
A1 Bague, Silvia
A1 Mayodormo-Aranda, Empar
A1 Vicioso, Luis
A1 Hernandez-Barcelo, Jose Emilio
A1 Rubio-Casadevall, Jordi
A1 de-Juan, Ana
A1 Fiaño-Valverde, Maria Concepcion
A1 Hindi, Nadia
A1 Lopez-Alvarez, Maria
A1 Lacerenza, Serena
A1 Dopazo, Joaquin
A1 Gutierrez, Antonio
A1 Alvarez, Rosa
A1 Valverde, Claudia
A1 Martinez-Trufero, Javier
A1 Martin-Broto, Javier
K1 gene signature
K1 predictive biomarkers
K1 trabectedin
AB 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.
PB John Wiley & Sons Ltd.
YR 2021
FD 2021-12-02
LK http://hdl.handle.net/10668/17787
UL http://hdl.handle.net/10668/17787
LA en
NO Moura DS, Peña-Chilet M, Cordero Varela JA, Alvarez-Alegret R, Agra-Pujol C, et al. A DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin. Mol Oncol. 2021 Dec;15(12):3691-3705.
NO This study was funded by the Spanish Group for Research on Sarcoma (GEIS) and partially by PharmaMar. The authors would like to thank the GEIS data center for data management. The authors also thank the donors and the Hospital Universitario Virgen del Rocío—Instituto de Biomedicina de Sevilla Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobancos PT17/0015/0041) for part of the human specimens used in this study. David S. Moura is recipient of a Sara Borrell postdoctoral fellowship funded by the National Institute of Health Carlos III (ISCIII) (CD20/00155).
DS RISalud
RD Apr 18, 2025