Gayarre, JavierKamieniak, Marta MCazorla-Jiménez, AliciaMuñoz-Repeto, IvanBorrego, SaludGarcía-Donas, JesúsHernando, SusanaRobles-Díaz, LuisGarcía-Bueno, José MRamón Y Cajal, TeresaHernández-Agudo, ElenaHeredia Soto, VictoriaMárquez-Rodas, IvanEcharri, María JoséLacambra-Calvet, CarmenSáez, RaquelCusidó, MaiteRedondo, AndrésPaz-Ares, LuisHardisson, DavidMendiola, MartaPalacios, JoséBenítez, JavierGarcía, María José2023-01-252023-01-252015-11-27http://hdl.handle.net/10668/10405We 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. 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 log-rank 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. 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. Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.enAttribution-NonCommercial 4.0 Internationalhttp://creativecommons.org/licenses/by-nc/4.0/6q24-26 DeletionCisplatin-SensitivityDNA RepairGTF2H5Ovarian Epithelial CancerSurvivalAdultAgedAged, 80 and overBiomarkers, TumorCarcinoma, Ovarian EpithelialCystadenocarcinoma, SerousFemaleGene Expression Regulation, NeoplasticHumansKaplan-Meier EstimateMiddle AgedNeoplasm GradingNeoplasm ProteinsNeoplasms, Glandular and EpithelialOvarian NeoplasmsPrognosisTranscription FactorsTumor Cells, Culturedresearch article26463438open access10.3802/jgo.2016.27.e72005-0399PMC4695457https://doi.org/10.3802/jgo.2016.27.e7https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695457/pdf