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.