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dc.contributor.authorGayarre, Javier-
dc.contributor.authorBorrego, Salud-
dc.contributor.authorPaz-Ares, Luis-
dc.contributor.authorPalacios Calvo, José-
dc.contributor.authorGarcía, M. José-
dc.identifiere-issn: 2005-0399-
dc.identifierissn: 2005-0380-
dc.identifier.citationJournal of Gynecologic Oncology 27(1): e7 (2016)-
dc.descriptionGayarre, Javier et al-
dc.description.abstract[Objective] We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients.-
dc.description.abstract[Methods] In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and logrank test were used to estimate patients’ survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays.-
dc.description.abstract[Results] Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5-silenced ovarian cancer cells.-
dc.description.abstract[Conclusion] Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.-
dc.description.sponsorshipThis study was financially supported by the Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III (grant PI12/01319) and by FEDER funds (2014-2020 Program). MJG is recipient of a research contract from the Instituto de Salud Carlos III of the Ministerio Español de Sanidad y Consumo (Miguel Servet tipo II Program, CPII 13/00047). JG has a contract from CIBERER and MMK was a holder of a La Caixa international PhD fellowship. LPA and JP are recipients of financial support from Red Temática de Investigación Cooperativa en Cáncer (RTICC) (grants RD12/0036/0028 and RD12/0036/0064, respectively). Gayarre, Javier et al.-
dc.publisherAsian Society of Gynecologic Oncology-
dc.relation.isversionofPublisher's version-
dc.subject6q24-26 Deletion-
dc.subjectOvarian Epithelial Cancer-
dc.subjectDNA Repair-
dc.titleThe NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients-
dc.description.versionPeer Reviewed-
dc.contributor.funderRed Temática de Investigación Cooperativa en Cáncer (España)-
dc.contributor.funderObra Social la Caixa-
dc.contributor.funderEuropean Commission-
dc.contributor.funderCentro de Investigación Biomédica en Red Enfermedades Raras (España)-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderMinisterio de Sanidad, Servicios Sociales e Igualdad (España)-
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