2024-03-19T05:25:23Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1435202021-12-27T16:43:53Zcom_10261_11773com_10261_1col_10261_11774
2017-02-07T08:29:08Z
urn:hdl:10261/143520
The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients
Gayarre, Javier
Borrego, Salud
Paz-Ares, Luis
Palacios Calvo, José
García, M. José
Red Temática de Investigación Cooperativa en Cáncer (España)
Fundación "la Caixa"
European Commission
Centro de Investigación Biomédica en Red Enfermedades Raras (España)
Instituto de Salud Carlos III
Ministerio de Sanidad, Servicios Sociales e Igualdad (España)
6q24-26 Deletion
Survival
Ovarian Epithelial Cancer
Cisplatin-Sensitivity
DNA Repair
GTF2H5
Gayarre, Javier et al
[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 ≤ 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.
[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.
2017-02-07T08:29:08Z
2017-02-07T08:29:08Z
2016-01
2017-02-07T08:29:09Z
artículo
Journal of Gynecologic Oncology 27(1): e7 (2016)
http://hdl.handle.net/10261/143520
10.3802/jgo.2016.27.e7
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100003751
26463438
eng
Publisher's version
http://doi.org/10.3802/jgo.2016.27.e7
Sí
http://creativecommons.org/licenses/by-nc/4.0/
openAccess
Asian Society of Gynecologic Oncology