Abstract
BackgroundProtein tyrosine phosphatase type IVA member 3 (PTP4A3/PRL-3), a metastasis-associated phosphatase, plays multiple roles in cancer metastasis. We investigated PTP4A3/PRL-3 expression and its correlation with the clinicopathological features and prognosis in hepatocellular carcinoma (HCC).MethodsGene expression profiles of PTP4A3/PRL-3 were obtained in poorly differentiated HCC tissues. The results were validated independently by TaqMan gene expression assays and immunohistochemical analysis.ResultsAccording to the microarray profiles, PTP4A3/PRL-3 was upregulated in patients with poorly differentiated disease compared to patients with well-differentiated disease with hepatic backgrounds associated with hepatitis B or C. Validation analysis showed that the PTP4A3/PRL-3 mRNA and protein levels were significantly associated with poor differentiation (P < 0.0001), high serum α-fetoprotein (P < 0.01), high serum protein induced by vitamin K absence/antagonist-II (PIVKA-II), and hepatic vascular invasion (P < 0.05). The expression of PTP4A3/PRL-3 protein was also correlated with advanced cancer stages (P < 0.01); this resulted in a significantly poorer prognosis in both overall (P = 0.0024) and recurrence-free survival (P = 0.0227). According Cox regression univariate analysis, the positive expression of PTP4A3/PRL-3 was a poor risk prognostic factor (OS, P = 0.0031; recurrence-free survival, P = 0.0245). Cox regression multivariate analysis indicated that high PTP4A3/PRL-3 expression was an independent, unfavorable prognostic factor for overall survival (hazard ratio 0.542; P = 0.048).ConclusionsPTP4A3/PRL-3 might be closely associated with HCC progression, invasion, and metastasis. Its high expression had a negative impact on the prognosis of HCC patients. This strongly suggests that PTP4A3/PRL-3 should be considered as a prognostic factor. Further analysis should be pursued to evaluate it as a novel prognostic target.Electronic supplementary materialThe online version of this article (doi:10.1245/s10434-012-2395-2) contains supplementary material, which is available to authorized users.
Highlights
Protein tyrosine phosphatase type IVA member 3 (PTP4A3/phosphatase of regenerating liver-3 (PRL-3)), a metastasis-associated phosphatase, plays multiple roles in cancer metastasis
The gene expression analysis was performed for 15 hepatocellular carcinoma (HCC) cases associated with hepatitis B virus (HBV) (Fig. 1a) and 27 HCCs associated with hepatitis C virus (HCV) (Fig. 1b) according to a well or poor differentiation status of the tumor, respectively
We studied the significance of PTP4A3/PRL-3 mRNA and protein expression, from a clinical viewpoint, for the progression of HCC
Summary
Protein tyrosine phosphatase type IVA member 3 (PTP4A3/PRL-3), a metastasis-associated phosphatase, plays multiple roles in cancer metastasis. We investigated PTP4A3/PRL-3 expression and its correlation with the clinicopathological features and prognosis in hepatocellular carcinoma (HCC). Gene expression profiles of PTP4A3/PRL-3 were obtained in poorly differentiated HCC tissues. The results were validated independently by TaqMan gene expression assays and immunohistochemical analysis. According to the microarray profiles, PTP4A3/ PRL-3 was upregulated in patients with poorly differentiated disease compared to patients with well-differentiated disease with hepatic backgrounds associated with hepatitis B or C. Validation analysis showed that the PTP4A3/PRL3 mRNA and protein levels were significantly associated with poor differentiation (P \ 0.0001), high serum a-fetoprotein (P \ 0.01), high serum protein induced by vitamin K absence/antagonist-II (PIVKA-II), and hepatic vascular invasion (P \ 0.05). The expression of PTP4A3/ PRL-3 protein was correlated with advanced cancer
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