The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients / 부인종양
Journal of Gynecologic Oncology
;
: e7-2016.
Artículo
en Inglés
| WPRIM
| ID: wpr-21469
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.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Neoplasias Ováricas
/
Pronóstico
/
Factores de Transcripción
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Células Tumorales Cultivadas
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Biomarcadores de Tumor
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Regulación Neoplásica de la Expresión Génica
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Cistadenocarcinoma Seroso
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Neoplasias Glandulares y Epiteliales
/
Estimación de Kaplan-Meier
/
Clasificación del Tumor
Tipo de estudio:
Estudio pronóstico
Límite:
Adulto
/
Anciano
/
Aged80
/
Femenino
/
Humanos
Idioma:
Inglés
Revista:
Journal of Gynecologic Oncology
Año:
2016
Tipo del documento:
Artículo
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