title: Expression of partitioning defective 3 (Par-3) for predicting extrahepatic metastasis and survival with hepatocellular carcinoma.
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.
authors: Department of Pathology and Laboratory Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan. jliou@nhri.org.tw.
authors: Yee-Jee
authors: YJ
authors: Jan
authors: Bor-Sheng
authors: BS
authors: Ko
authors: Tzu-An
authors: TA
authors: Liu
authors: Yao-Ming
authors: YM
authors: Wu
authors: Shu-Man
authors: SM
authors: Liang
authors: Shyh-Chang
authors: SC
authors: Chen
authors: John
authors: J
authors: Wang
authors: Jun-Yang
authors: JY
authors: Liou
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D048948:14-3-3 Proteins; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human