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oai:repisalud.isciii.es:20.500.12105/229622024-11-28T16:37:24Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16958col_20.500.12105_16967

00925njm 22002777a 4500 dc Moura, David S author Sanchez-Bustos, Paloma author Fernández-Serra, Antonio author Lopez-Alvarez, Maria author Mondaza-Hernandez, Jose L author Blanco-Alcaina, Elena author Gavilan-Naranjo, Angela author Martinez-Delgado, Paula author Lacerenza, Serena author Santos-Fernandez, Paloma author Carrasco-Garcia, Irene author Hidalgo-Rios, Samuel author Gutierrez, Antonio author Ramos-Asensio, Rafael author Hindi, Nadia author Taron, Miguel author Lopez-Guerrero, Jose Antonio author Martin-Broto, Javier author 2020-05 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. Moura DS, Sanchez-Bustos P, Fernandez-Serra A, Lopez-Alvarez M, Mondaza-Hernandez JL, Blanco-Alcaina E, et al. CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study. Cancers. 2020 May;12(5):1128. 10.3390/cancers12051128 2072-6694 Cancers http://hdl.handle.net/20.500.13003/10809 32365979 L2004275505 2-s2.0-85085001603 https://hdl.handle.net/20.500.12105/22962 539246000069 Trabectedin ERCC1 CUL4A Predictive biomarkers Soft-tissue sarcoma CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study