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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2021
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oai:doaj.org-article:97947f91b0b04bea97667fd90e9fbdb62021-12-02T10:31:06ZA DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin1878-02611574-789110.1002/1878-0261.12996https://doaj.org/article/97947f91b0b04bea97667fd90e9fbdb62021-12-01T00:00:00Zhttps://doi.org/10.1002/1878-0261.12996https://doaj.org/toc/1574-7891https://doaj.org/toc/1878-0261Predictive 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.David S. MouraMaria Peña‐ChiletJuan Antonio Cordero VarelaRamiro Alvarez‐AlegretCarolina Agra‐PujolFrancisco IzquierdoRafael RamosLuis Ortega‐MedinaFrancisco Martin‐DavilaCarolina Castilla‐RamirezCarmen Nieves Hernandez‐LeonCleofe RomagosaMaria Angeles Vaz SalgadoJavier LaverniaSilvia BaguéEmpar Mayodormo‐ArandaLuis ViciosoJose Emilio Hernández BarcelóJordi Rubio‐CasadevallAna deJuanMaria Concepcion Fiaño‐ValverdeNadia HindiMaria Lopez‐AlvarezSerena LacerenzaJoaquin DopazoAntonio GutierrezRosa AlvarezClaudia ValverdeJavier Martinez‐TruferoJavier Martín‐BrotoWileyarticlegene signaturepredictive biomarkerstrabectedinNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENMolecular Oncology, Vol 15, Iss 12, Pp 3691-3705 (2021) |
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| collection |
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| topic |
gene signature predictive biomarkers trabectedin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
gene signature predictive biomarkers trabectedin Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 David S. Moura Maria Peña‐Chilet Juan Antonio Cordero Varela Ramiro Alvarez‐Alegret Carolina Agra‐Pujol Francisco Izquierdo Rafael Ramos Luis Ortega‐Medina Francisco Martin‐Davila Carolina Castilla‐Ramirez Carmen Nieves Hernandez‐Leon Cleofe Romagosa Maria Angeles Vaz Salgado Javier Lavernia Silvia Bagué Empar Mayodormo‐Aranda Luis Vicioso Jose Emilio Hernández Barceló Jordi Rubio‐Casadevall Ana deJuan Maria Concepcion Fiaño‐Valverde Nadia Hindi Maria Lopez‐Alvarez Serena Lacerenza Joaquin Dopazo Antonio Gutierrez Rosa Alvarez Claudia Valverde Javier Martinez‐Trufero Javier Martín‐Broto A DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| description |
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. |
| format |
article |
| author |
David S. Moura Maria Peña‐Chilet Juan Antonio Cordero Varela Ramiro Alvarez‐Alegret Carolina Agra‐Pujol Francisco Izquierdo Rafael Ramos Luis Ortega‐Medina Francisco Martin‐Davila Carolina Castilla‐Ramirez Carmen Nieves Hernandez‐Leon Cleofe Romagosa Maria Angeles Vaz Salgado Javier Lavernia Silvia Bagué Empar Mayodormo‐Aranda Luis Vicioso Jose Emilio Hernández Barceló Jordi Rubio‐Casadevall Ana deJuan Maria Concepcion Fiaño‐Valverde Nadia Hindi Maria Lopez‐Alvarez Serena Lacerenza Joaquin Dopazo Antonio Gutierrez Rosa Alvarez Claudia Valverde Javier Martinez‐Trufero Javier Martín‐Broto |
| author_facet |
David S. Moura Maria Peña‐Chilet Juan Antonio Cordero Varela Ramiro Alvarez‐Alegret Carolina Agra‐Pujol Francisco Izquierdo Rafael Ramos Luis Ortega‐Medina Francisco Martin‐Davila Carolina Castilla‐Ramirez Carmen Nieves Hernandez‐Leon Cleofe Romagosa Maria Angeles Vaz Salgado Javier Lavernia Silvia Bagué Empar Mayodormo‐Aranda Luis Vicioso Jose Emilio Hernández Barceló Jordi Rubio‐Casadevall Ana deJuan Maria Concepcion Fiaño‐Valverde Nadia Hindi Maria Lopez‐Alvarez Serena Lacerenza Joaquin Dopazo Antonio Gutierrez Rosa Alvarez Claudia Valverde Javier Martinez‐Trufero Javier Martín‐Broto |
| author_sort |
David S. Moura |
| title |
A DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| title_short |
A DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| title_full |
A DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| title_fullStr |
A DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| title_full_unstemmed |
A DNA damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| title_sort |
dna damage repair gene‐associated signature predicts responses of patients with advanced soft‐tissue sarcoma to treatment with trabectedin |
| publisher |
Wiley |
| publishDate |
2021 |
| url |
https://doaj.org/article/97947f91b0b04bea97667fd90e9fbdb6 |
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