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Int. J. Mol. Sci. 2013, 14(1), 1684-1697; doi:10.3390/ijms14011684
Article

Expression of Partitioning Defective 3 (Par-3) for Predicting Extrahepatic Metastasis and Survival with Hepatocellular Carcinoma

1,†
,
2,3,†
,
2,†
,
4
,
2
,
1
,
1
 and
2,5,*
1 Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan 2 Institute of Cellular and System Medicine, National Health Research Institutes, Zhunan 350, Taiwan 3 Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan 4 Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan 5 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 / Revised: 4 January 2013 / Accepted: 6 January 2013 / Published: 15 January 2013
(This article belongs to the Special Issue Advances in Cancer Diagnosis)
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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 hepatocellular carcinoma; metastasis; Par-3; survival
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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