03079nas a2200493 4500008004100000022001400041245014600055210006900201260001200270300001400282490000700296520140800303100002001711700002401731700002901755700002801784700002501812700002501837700001801862700002401880700002901904700003101933700003501964700002101999700003102020700002102051700001902072700002802091700001802119700003102137700002802168700001702196700003902213700001702252700002502269700002202294700002002316700002302336700001802359700002202377700002902399700002502428856013202453 2021 eng d a1878-026100aA DNA damage repair gene-associated signature predicts responses of patients with advanced soft-tissue sarcoma to treatment with trabectedin.0 aDNA damage repair geneassociated signature predicts responses of c2021 12 a3691-37050 v153 a
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.
1 aMoura, David, S1 aPeña-Chilet, Maria1 aVarela, Juan, Antonio Co1 aAlvarez-Alegret, Ramiro1 aAgra-Pujol, Carolina1 aIzquierdo, Francisco1 aRamos, Rafael1 aOrtega-Medina, Luis1 aMartin-Davila, Francisco1 aCastilla-Ramirez, Carolina1 aHernandez-Leon, Carmen, Nieves1 aRomagosa, Cleofe1 aSalgado, Maria, Angeles Va1 aLavernia, Javier1 aBagué, Silvia1 aMayodormo-Aranda, Empar1 aVicioso, Luis1 aBarceló, Jose, Emilio Her1 aRubio-Casadevall, Jordi1 ade Juan, Ana1 aFiaño-Valverde, Maria, Concepcion1 aHindi, Nadia1 aLopez-Alvarez, Maria1 aLacerenza, Serena1 aDopazo, Joaquin1 aGutierrez, Antonio1 aAlvarez, Rosa1 aValverde, Claudia1 aMartinez-Trufero, Javier1 aMartin-Broto, Javier uhttps://clinbioinfosspa.es/content/dna-damage-repair-gene-associated-signature-predicts-responses-patients-advanced-soft-tissue