CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study

A translational study was designed to analyze the expression of nucleotide excision repair (NER) and homologous recombination (HR) genes as potential predictive biomarkers for trabectedin in soft-tissue sarcoma (STS). This study is part of a randomized phase II trial comparing trabectedin plus doxor...

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Detalles Bibliográficos
Autores: Moura, David S., Sanchez-Bustos, Paloma, Fernández-Serra, Antonio, Lopez-Alvarez, Maria, Mondaza-Hernandez, Jose L., Blanco-Alcaina, Elena, Gavilan-Naranjo, Angela, Martinez-Delgado, Paula, Lacerenza, Serena, Santos-Fernandez, Paloma, Carrasco-Garcia, Irene, Hidalgo-Rios, Samuel, Gutiérrez, Antonio, Ramos-Asensio, Rafael, Hindi, Nadia, Taron, Miguel, Lopez-Guerrero, Jose Antonio, Martin-Broto, Javier
Tipo de recurso: artículo
Fecha de publicación:2020
País:España
Institución:Conselleria de Salut i Consum del Govern de les Illes Balears
Repositorio:Docusalut
Idioma:inglés
OAI Identifier:oai:docusalut.com:20.500.13003/10809
Acceso en línea:https://hdl.handle.net/20.500.13003/10809
Access Level:acceso abierto
Palabra clave:trabectedin
ERCC1
CUL4A
predictive biomarkers
soft-tissue sarcoma
Descripción
Sumario:A translational study was designed to analyze the expression of nucleotide excision repair (NER) and homologous recombination (HR) genes as potential predictive biomarkers for trabectedin in soft-tissue sarcoma (STS). This study is part of a randomized phase II trial comparing trabectedin plus doxorubicin versus doxorubicin in advanced STS. Gene expression levels were evaluated by qRT-PCR, while CUL4A protein levels were quantified by immunohistochemistry. Expression levels were correlated with patients' progression-free survival (PFS) and overall survival (OS). Gene expression was also evaluated in cell lines and correlated with trabectedin sensitivity. In doxorubicin arm and in the whole series, which includes samples from both arms, no significant differences in terms of PFS were observed amongst the analyzed genes. In the group treated with trabectedin plus doxorubicin, the median of PFS was significantly longer in cases with CUL4A, ERCC1, or ERCC5 overexpression, while BRCA1 expression did not correlated with PFS. Gene expression had no prognostic influence in OS. CUL4A protein levels correlated with worse PFS in doxorubicin arm and in the whole series. In cell lines, only overexpression of ERCC1 was significantly correlated with trabectedin sensitivity. In conclusion, CUL4A, ERCC5, and mainly ERCC1 acted as predictive factors for trabectedin efficacy in advanced STS.

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