The aim of this study is to evaluate the biological role and clinical implications of
silent mating type information regulation 2 homolog 1 (
SIRT1) as a novel candidate for target
therapy in
triple negative breast cancer (TNBC) for which there is no specific agent. 344 patients who received surgical resection for TNBC from January 2003 to December 2006 at Seoul National University Hospital were enrolled, and the role of
SIRT1 protein was evaluated via immunohistochemistry on tissue samples. In vivo experiments to evaluate
tumor invasiveness were carried out with three human TNBC cell lines following SIRT1-siRNA transfection. Expression of
SIRT1 significantly correlated with
lymph node metastasis (p = 0.008). In multivariate analysis,
SIRT1 expression (p = 0.011), T stage (p = 0.014), and lymphatic invasion (p < 0.001) were revealed to be independent predictive factors for
lymph node metastasis. Combination of these three parameters revealed predictive performance for
lymph node metastasis with an area under the curve (AUC) of 0.689 on receiver operating characteristics (ROC) curves analysis.
SIRT1 expression correlated with shorter disease-free survival (P = 0.003) but not with overall survival. Inhibition of
SIRT1 with
small interfering RNA (
siRNA) conspicuously suppressed the invasiveness of TNBC cell lines. This study reveals the role of
SIRT1 on
tumor invasiveness and unfavorable clinical outcomes, and we suggest its potential role as a prognostic
indicator as well as a novel therapeutic target in TNBC.