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Title: The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.
Authors: Gayarre, Javier
Kamieniak, Marta M
Cazorla-Jiménez, Alicia
Muñoz-Repeto, Ivan
Borrego, Salud
García-Donas, Jesús
Hernando, Susana
Robles-Díaz, Luis
García-Bueno, José M
Ramón Y Cajal, Teresa
Hernández-Agudo, Elena
Heredia Soto, Victoria
Márquez-Rodas, Ivan
Echarri, María José
Lacambra-Calvet, Carmen
Sáez, Raquel
Cusidó, Maite
Redondo, Andrés
Paz-Ares, Luis
Hardisson, David
Mendiola, Marta
Palacios, José
Benítez, Javier
García, María José
Keywords: 6q24-26 Deletion;Cisplatin-Sensitivity;DNA Repair;GTF2H5;Ovarian Epithelial Cancer;Survival
metadata.dc.subject.mesh: Adult
Aged, 80 and over
Biomarkers, Tumor
Carcinoma, Ovarian Epithelial
Cystadenocarcinoma, Serous
Gene Expression Regulation, Neoplastic
Kaplan-Meier Estimate
Middle Aged
Neoplasm Grading
Neoplasm Proteins
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Transcription Factors
Tumor Cells, Cultured
Issue Date: 27-Nov-2015
Abstract: 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. 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.
metadata.dc.identifier.doi: 10.3802/jgo.2016.27.e7
Appears in Collections:Producción 2020

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