NDRG2 is involved in the oncogenic properties of renal cell carcinoma and its loss is a novel independent poor prognostic factor after nephrectomy.
Ann Surg Oncol
; 19(8): 2763-72, 2012 Aug.
Article
em En
| MEDLINE
| ID: mdl-22246425
ABSTRACT
BACKGROUND:
Although NDRG2 is a candidate tumor suppressor, its exact role in renal cell carcinoma (RCC) is not fully understood. We investigated the functional role of NDRG2 and its clinical relevance in RCC tumorigenesis.METHODS:
NDRG2 expression and its clinical implications in clear cell RCC were evaluated. Biological function was assessed by a proliferation assay, anchorage-independent growth assay, and wound healing and transwell migration assays in RCC cell lines overexpressing NDRG2 coupled with an investigation of the effects of NDRG2 expression on the epithelial-mesenchymal transition (EMT).RESULTS:
NDRG2 was differentially expressed in patients with RCC. A loss of NDRG2 was significantly associated with a higher proportion of tumors >10 cm and a high nuclear grade. Furthermore, multivariate analyses indicated that a loss of NDRG2 was an independent poor prognostic factor for patient survival (recurrence-free survival, hazard ratio 7.901; disease-specific survival, hazard ratio 15.395; overall survival, hazard ratio 11.339; P < 0.001 for all parameters). NDRG2 expression inhibited the anchorage-independent growth and migration of RCC cells. NDRG2 expression also modulated the expression of EMT-related genes such as Snail, Slug, and SIP1, and it decreased EMT signaling in RCC cells. Finally, NDRG2 recovered E-cadherin expression in E-cadherin-negative RCC cells.CONCLUSIONS:
These results indicate that a lack of NDRG2 is associated with oncogenic properties through the loss of its role as a tumor suppressor, and that NDRG2 is an independent poor prognostic factor predicting survival in clear cell RCC, suggesting that it can serve as a novel prognostic biomarker.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Complicações Pós-Operatórias
/
Carcinoma de Células Renais
/
Transformação Celular Neoplásica
/
Proteínas Supressoras de Tumor
/
Neoplasias Renais
/
Recidiva Local de Neoplasia
/
Nefrectomia
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article