Upregulation of protein tyrosine phosphatase type IVA member 3 (PTP4A3/PRL-3) is associated with tumor differentiation and a poor prognosis in human hepatocellular carcinoma

Abudureheman Mayinuer, Mahmut Yasen, Kaoru Mogushi, Gulanbar Obulhasim, Maimaiti Xieraili, Arihiro Aihara, Shinji Tanaka, Hiroshi Mizushima, Hiroshi Tanaka, Shigeki Arii

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Background: 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). Methods: 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. Results: 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/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). Conclusions: PTP4A3/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.

Original languageEnglish
Pages (from-to)305-317
Number of pages13
JournalAnnals of Surgical Oncology
Volume20
Issue number1
DOIs
Publication statusPublished - 2013 Jan

ASJC Scopus subject areas

  • Surgery
  • Oncology

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