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The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.

dc.contributor.authorGayarre, Javier
dc.contributor.authorKamieniak, Marta M
dc.contributor.authorCazorla-Jiménez, Alicia
dc.contributor.authorMuñoz-Repeto, Ivan
dc.contributor.authorBorrego, Salud
dc.contributor.authorGarcía-Donas, Jesús
dc.contributor.authorHernando, Susana
dc.contributor.authorRobles-Díaz, Luis
dc.contributor.authorGarcía-Bueno, José M
dc.contributor.authorRamón Y Cajal, Teresa
dc.contributor.authorHernández-Agudo, Elena
dc.contributor.authorHeredia Soto, Victoria
dc.contributor.authorMárquez-Rodas, Ivan
dc.contributor.authorEcharri, María José
dc.contributor.authorLacambra-Calvet, Carmen
dc.contributor.authorSáez, Raquel
dc.contributor.authorCusidó, Maite
dc.contributor.authorRedondo, Andrés
dc.contributor.authorPaz-Ares, Luis
dc.contributor.authorHardisson, David
dc.contributor.authorMendiola, Marta
dc.contributor.authorPalacios, José
dc.contributor.authorBenítez, Javier
dc.contributor.authorGarcía, María José
dc.date.accessioned2023-01-25T08:36:04Z
dc.date.available2023-01-25T08:36:04Z
dc.date.issued2015-11-27
dc.description.abstractWe 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.
dc.identifier.doi10.3802/jgo.2016.27.e7
dc.identifier.essn2005-0399
dc.identifier.pmcPMC4695457
dc.identifier.pmid26463438
dc.identifier.pubmedURLhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4695457/pdf
dc.identifier.unpaywallURLhttps://doi.org/10.3802/jgo.2016.27.e7
dc.identifier.urihttp://hdl.handle.net/10668/10405
dc.issue.number1
dc.journal.titleJournal of gynecologic oncology
dc.journal.titleabbreviationJ Gynecol Oncol
dc.language.isoen
dc.organizationInstituto de Biomedicina de Sevilla-IBIS
dc.organizationHospital Universitario Virgen del Rocío
dc.page.numbere7
dc.pubmedtypeJournal Article
dc.pubmedtypeMulticenter Study
dc.pubmedtypeResearch Support, Non-U.S. Gov't
dc.rightsAttribution-NonCommercial 4.0 International
dc.rights.accessRightsopen access
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subject6q24-26 Deletion
dc.subjectCisplatin-Sensitivity
dc.subjectDNA Repair
dc.subjectGTF2H5
dc.subjectOvarian Epithelial Cancer
dc.subjectSurvival
dc.subject.meshAdult
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshBiomarkers, Tumor
dc.subject.meshCarcinoma, Ovarian Epithelial
dc.subject.meshCystadenocarcinoma, Serous
dc.subject.meshFemale
dc.subject.meshGene Expression Regulation, Neoplastic
dc.subject.meshHumans
dc.subject.meshKaplan-Meier Estimate
dc.subject.meshMiddle Aged
dc.subject.meshNeoplasm Grading
dc.subject.meshNeoplasm Proteins
dc.subject.meshNeoplasms, Glandular and Epithelial
dc.subject.meshOvarian Neoplasms
dc.subject.meshPrognosis
dc.subject.meshTranscription Factors
dc.subject.meshTumor Cells, Cultured
dc.titleThe NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.
dc.typeresearch article
dc.type.hasVersionVoR
dc.volume.number27
dspace.entity.typePublication

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