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.
retrospective_cohort · Level III
Where this comes from
- Record sourced from PubMed, PMID 23064776.
- Also identified by DOI 10.1245/s10434-012-2395-2 and PMC identifier 3528959.
- Licence recorded as CC BY.
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Abstract
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/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). 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.
Medical subject headings
- Carcinoma, Hepatocellular
- Liver Neoplasms
- Neoplasm Proteins
- Protein Tyrosine Phosphatases
- Up-Regulation