RT Journal Article
T1 CUL4A, ERCC5, and ERCC1 as Predictive Factors for Trabectedin Efficacy in Advanced Soft Tissue Sarcomas (STS): A Spanish Group for Sarcoma Research (GEIS) Study.
A1 Moura, David S
A1 Sanchez-Bustos, Paloma
A1 Fernandez-Serra, Antonio
A1 Lopez-Alvarez, María
A1 Mondaza-Hernandez, José L
A1 Blanco-Alcaina, Elena
A1 Gavilan-Naranjo, Angela
A1 Martinez-Delgado, Paula
A1 Lacerenza, Serena
A1 Santos-Fernandez, Paloma
A1 Carrasco-Garcia, Irene
A1 Hidalgo-Rios, Samuel
A1 Gutierrez, Antonio
A1 Ramos, Rafael
A1 Hindi, Nadia
A1 Taron, Miguel
A1 Lopez-Guerrero, Jose Antonio
A1 Martin-Broto, Javier
K1 CUL4A
K1 ERCC1
K1 predictive biomarkers
K1 soft-tissue sarcoma
K1 trabectedin
AB 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.
SN 2072-6694
YR 2020
FD 2020-04-30
LK https://hdl.handle.net/10668/27887
UL https://hdl.handle.net/10668/27887
LA en
DS RISalud
RD Apr 6, 2025