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Oncogenic role of SIRT1 associated with tumor invasion, lymph node metastasis, and poor disease-free survival in triple negative breast cancer

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Abstract

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.

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Acknowledgments

This work was supported by the Dongnam Institute of Radiological & Medical Sciences (DIRAMS) grant funded by the Korea government (MSIP) (Grant No. 50608-2015) and by Grant No. 03-2014-0380 from Seoul National University Hospital Research Fund.

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    Authors and Affiliations

    1. Department of Pathology, Cancer Center, Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan, South Korea

      Soo Young Chung

    2. Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul, Korea

      Yoon Yang Jung

    3. Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

      In Ae Park, Hyojin Kim, Yul Ri Chung, Ji Young Kim, Soo Young Park, Chul Lee & Han Suk Ryu

    4. Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

      Seock-Ah Im, Kyung-Hun Lee & Tae-Yong Kim

    5. Department of Surgery, Seoul National University Hospital, Seoul, Korea

      Hyeong-Gon Moon, Dong-Young Noh & Wonshik Han

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    1. Soo Young Chung
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    Correspondence to Han Suk Ryu.

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    Soo Young Chung and Yoon Yang Jung made equal contributions to this work.

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    Chung, S.Y., Jung, Y.Y., Park, I.A. et al. Oncogenic role of SIRT1 associated with tumor invasion, lymph node metastasis, and poor disease-free survival in triple negative breast cancer. Clin Exp Metastasis 33, 179–185 (2016). https://doi.org/10.1007/s10585-015-9767-5

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    • DOI: https://doi.org/10.1007/s10585-015-9767-5

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