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Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma
Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan
Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 350, Taiwan
Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan
Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan
Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan
These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 23 November 2012; in revised form: 4 January 2013 / Accepted: 6 January 2013 / Published: 15 January 2013
Abstract: Partitioning defective 3 (Par-3), a crucial component of partitioning-defective complex proteins, controls cell polarity and contributes to cell migration and cancer cell epithelial-to-mesenchymal transition. However, the clinical relevance of Par-3 in tumor progression and metastasis has not been well elucidated. In this study, we investigated the impact and association of Par-3 expression and clinical outcomes with hepatocellular carcinoma (HCC). We first confirmed that Par-3 was abundantly expressed in HCC cell lines by Western blot analysis. We used immunohistochemistry to analyze the association of Par-3 expression and clinicopathological characteristics in primary and subsequent metastatic tumors of patients with HCC. Par-3 was overexpressed in 47 of 111 (42.3%) primary tumors. Increased expression of Par-3 in primary tumors predicted an increased five-year cumulative incidence of extrahepatic metastasis. In addition, multivariate analysis revealed that Par-3 overexpression was an independent risk factor of extrahepatic metastasis. Increased Par-3 expression in primary tumors was associated with poor five-year overall survival rates and was an independent prognostic factor on Cox regression analysis. In conclusion, we show for the first time that increased Par-3 expression is associated with distant metastasis and poor survival rates in patients with HCC. Par-3 may be a novel prognostic biomarker and therapeutic target for HCC.
Keywords: hepatocellular carcinoma; metastasis; Par-3; survival
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Jan, Y.-J.; Ko, B.-S.; Liu, T.-A.; Wu, Y.-M.; Liang, S.-M.; Chen, S.-C.; Wang, J.; Liou, J.-Y. Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma. Int. J. Mol. Sci. 2013, 14, 1684-1697.
Jan Y-J, Ko B-S, Liu T-A, Wu Y-M, Liang S-M, Chen S-C, Wang J, Liou J-Y. Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma. International Journal of Molecular Sciences. 2013; 14(1):1684-1697.
Jan, Yee-Jee; Ko, Bor-Sheng; Liu, Tzu-An; Wu, Yao-Ming; Liang, Shu-Man; Chen, Shyh-Chang; Wang, John; Liou, Jun-Yang. 2013. "Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma." Int. J. Mol. Sci. 14, no. 1: 1684-1697.