The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients
| العنوان: | The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients |
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| المؤلفون: | Gayarre, Javier, Kamieniak, Marta M., Cazorla-Jiménez, Alicia, Muñoz-Repeto, Ivan, Borrego, Salud, García-Donas, Jesús, Hernando, Susana, Robles-Díaz, Luis, García-Bueno, José María, Ramon 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, Benitez, Javier, Garcia, Maria José, Universitat Autònoma de Barcelona. Departament de Medicina |
| المساهمون: | 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) |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname Journal of Gynecologic Oncology Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid |
| بيانات النشر: | Asian Society of Gynecologic Oncology; Korean Society of Gynecologic Oncology and Colposcopy, 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, Survival, DNA Repair, endocrine system diseases, 6q24-26 Deletion, Kaplan-Meier Estimate, Carcinoma, Ovarian Epithelial, Ovarian epithelial cancer, 0302 clinical medicine, Tumor Cells, Cultured, Serous ovarian cancer, Neoplasms, Glandular and Epithelial, Related gene, Aged, 80 and over, Ovarian Neoplasms, Obstetrics and Gynecology, General Medicine, Middle Aged, Prognosis, Predictive value, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, Female, Original Article, Adult, medicine.medical_specialty, DNA repair, Ovarian Epithelial Cancer, Cisplatin sensitivity, 03 medical and health sciences, Internal medicine, Translational Research, Biomarkers, Tumor, medicine, Humans, Cisplatin-Sensitivity, Gene, Aged, Neoplasm Grading, business.industry, Cystadenocarcinoma, Serous, GTF2H5, 030104 developmental biology, business, Transcription Factors |
| الوصف: | 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. This study was financially supported by the Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III (grant PI12/01319) and by FEDER funds (2014-2020 Program). MJG is recipient of a research contract from the Instituto de Salud Carlos III of the Ministerio Español de Sanidad y Consumo (Miguel Servet tipo II Program, CPII 13/00047). JG has a contract from CIBERER and MMK was a holder of a La Caixa international PhD fellowship. LPA and JP are recipients of financial support from Red Temática de Investigación Cooperativa en Cáncer (RTICC) (grants RD12/0036/0028 and RD12/0036/0064, respectively). Gayarre, Javier et al. |
| وصف الملف: | application/pdf |
| تدمد: | 2005-0399 2005-0380 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b0f1c4e007ad7351fb3dcb9da441924cTest https://doi.org/10.3802/jgo.2016.27.e7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b0f1c4e007ad7351fb3dcb9da441924c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20050399 20050380 |
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