The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients.
- Author:
Javier GAYARRE
1
;
Marta M KAMIENIAK
;
Alicia CAZORLA-JIMENEZ
;
Ivan MUNOZ-REPETO
;
Salud BORREGO
;
Jesus GARCIA-DONAS
;
Susana HERNANDO
;
Luis ROBLES-DIAZ
;
Jose M GARCIA-BUENO
;
Teresa RAMON Y CAJAL
;
Elena HERNANDEZ-AGUDO
;
Victoria HEREDIA SOTO
;
Ivan MARQUEZ-RODAS
;
Maria Jose ECHARRI
;
Carmen LACAMBRA-CALVET
;
Raquel SAEZ
;
Maite CUSIDO
;
Andres REDONDO
;
Luis PAZ-ARES
;
David HARDISSON
;
Marta MENDIOLA
;
Jose PALACIOS
;
Javier BENITEZ
;
Maria Jose GARCIA
Author Information
- Publication Type:Original Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
- Keywords: Cisplatin-Sensitivity; DNA Repair; GTF2H5; Ovarian Epithelial Cancer; Survival; 6q24-26 Deletion
- MeSH: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor/biosynthesis/genetics; Cystadenocarcinoma, Serous/*genetics/metabolism/pathology; Female; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Middle Aged; Neoplasm Grading; Neoplasm Proteins/biosynthesis/genetics; Neoplasms, Glandular and Epithelial/*genetics/metabolism/pathology; Ovarian Neoplasms/*genetics/metabolism/pathology; Prognosis; Transcription Factors/biosynthesis/*genetics; Tumor Cells, Cultured
- From:Journal of Gynecologic Oncology 2016;27(1):e7-
- CountryRepublic of Korea
- Language:English
- 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. 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 < or = 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. 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. CONCLUSION: Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.
