Nrf2 overexpression predicts prognosis and 5-FU resistance in gastric cancer.
Asian Pac J Cancer Prev
; 14(9): 5231-5, 2013.
Article
en En
| MEDLINE
| ID: mdl-24175806
ABSTRACT
OBJECTIVE:
NF-E2-related factor 2 (Nrf2) is activated in several human malignancies. However, the role of Nrf2 in gastric cancer (GC) remains incompletely understood. In this study, we therefore analyzed associations of Nrf2 expression status with clinical features and chemotherapeutic resistance in GC. MATERIALS ANDMETHODS:
A total of 186 samples from GC patients who underwent gastrectomy were used for prognostic assessment. A further 142 samples from GC cases who received first-line combination chemotherapy were applied for investigation of chemoresistance. The Nrf2 expression was evaluated by immunohistochemistry in GC samples, and its relationship with clinicopathological parameters and chemotherapy sensitivity was analyzed. The effect of Nrf2 gene silencing on chemotherapy resistance was also examined by cell viability assay in vivo.RESULTS:
Of the 186 patients with GC, 104/186 (55.9%) showed high expression for Nrf2. The overexpression of Nrf2 was an independent predictor of overall survival [OS, hazard ratio (HR) 3.9; P=0.011] and disease-free survival (DFS, HR 4.3; P=0.002). The gene silencing of Nrf2 reduced resistance to cell death induced by 5-FU in GC cell lines.CONCLUSION:
Our data show that Nrf2 is an independent prognostic factor in GC. Furthermore, Nrf2 confers resistance to chemotherapeutic drug 5-FU in GC cells. Taken together, Nrf2 is a potential prognostic marker and predictive for 5-FU resistance in GC.
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Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_digestive_diseases
/
6_stomach_cancer
Asunto principal:
Neoplasias Gástricas
/
Adenocarcinoma
/
Biomarcadores de Tumor
/
Regulación Neoplásica de la Expresión Génica
/
Resistencia a Antineoplásicos
/
Factor 2 Relacionado con NF-E2
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Asian Pac J Cancer Prev
Asunto de la revista:
NEOPLASIAS
Año:
2013
Tipo del documento:
Article