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Open Access 01-01-2013 | Hepatobiliary Tumors

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

Authors: Abudureheman Mayinuer, MD, Mahmut Yasen, MD, PhD, Kaoru Mogushi, PhD, Gulanbar Obulhasim, MD, PhD, Maimaiti Xieraili, MD, Arihiro Aihara, MD, PhD, Shinji Tanaka, MD, PhD, Hiroshi Mizushima, PhD, Hiroshi Tanaka, PhD, Shigeki Arii, MD, PhD, FACS

Published in: Annals of Surgical Oncology | Issue 1/2013

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.

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Title: 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
Authors: Abudureheman Mayinuer, MD
Mahmut Yasen, MD, PhD
Kaoru Mogushi, PhD
Gulanbar Obulhasim, MD, PhD
Maimaiti Xieraili, MD
Arihiro Aihara, MD, PhD
Shinji Tanaka, MD, PhD
Hiroshi Mizushima, PhD
Hiroshi Tanaka, PhD
Shigeki Arii, MD, PhD, FACS
Publication date: 01-01-2013
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 1/2013
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-012-2395-2

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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

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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