Open AccessA DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin
Author(s) -
Moura David S.,
PeñaChilet Maria,
Cordero Varela Juan Antonio,
AlvarezAlegret Ramiro,
AgraPujol Carolina,
Izquierdo Francisco,
Ramos Rafael,
OrtegaMedina Luis,
MartinDavila Francisco,
CastillaRamirez Carolina,
HernandezLeon Carmen Nieves,
Romagosa Cleofe,
Vaz Salgado Maria Angeles,
Lavernia Javier,
Bagué Silvia,
MayodormoAranda Empar,
Vicioso Luis,
Hernández Barceló Jose Emilio,
RubioCasadevall Jordi,
Juan Ana,
FiañoValverde Maria Concepcion,
Hindi Nadia,
LopezAlvarez Maria,
Lacerenza Serena,
Dopazo Joaquin,
Gutierrez Antonio,
Alvarez Rosa,
Valverde Claudia,
MartinezTrufero Javier,
MartínBroto Javier
Publication year - 2021
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.12996
Subject(s) - trabectedin , ercc1 , gene signature , soft tissue sarcoma , dna repair , medicine , gene , nucleotide excision repair , oncology , cancer research , sarcoma , biology , bioinformatics , gene expression , genetics , pathology
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.