Abstract
BackgroundPRL-3 is a member of phosphatases of regenerating liver family, characterized by phosphatase active domain and C-terminal prenylation motif. Overexpression of PRL-3 has been implicated in multiple cancers. Here we examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants.MethodsPRL-3 expression was analyzed immunohistochemically in 196 gastric cancer patients and 21 cases of liver metastasis. A series of wild type PRL-3 or its mutant plasmids were expressed in BGC823 cells to investigate the relationship between its catalytic activity, cellular localization and metastatic potential in vitro.ResultsPositive staining of PRL-3 was observed in 19.4% (38/196) gastric cancer tissues compared with 76.2% (16/21) in liver metastasis. Statistical analysis revealed that PRL-3 expression correlated with lymph node metastasis and vascular invasion (P < 0.05). Patients with high PRL-3 expression showed poorer 5-year overall survival (P = 0.011). Wild type PRL-3 expressing cells resulted in enhanced migration and invasion ability, which were greatly crippled in form of PRL-3(C104S) or PRL-3(ΔCAAX) mutants accompanied with its alteration in subcellular localization.ConclusionsMetastasis associated protein PRL-3 may serve as a potential prognostic biomarker in human gastric cancer. Both the phosphatase catalytic activity and cellular localization are critical for its function.
Highlights
Despite a decrease in incidence in recent decades, gastric cancer is still the second leading cause of cancerrelated death worldwide, especially for those in advanced stages with metastatic lesions that still has a rather poor outcome [1]
Association of Phosphatase of regenerating liver-3 (PRL-3) expression and clinicopathological factors PRL-3 expression in 196 primary gastric tumor specimens and 21 cases of liver metastasis was determined by immunohistochemistry
In the 21 paired samples of primary cancer and liver metastasis, consistency of PRL-3 expression is observed with positive rate of 57.1% (12/21) and 76.2% (16/21), respectively (P < 0.05)
Summary
Despite a decrease in incidence in recent decades, gastric cancer is still the second leading cause of cancerrelated death worldwide, especially for those in advanced stages with metastatic lesions that still has a rather poor outcome [1]. As clinicians move towards personalized cancer medicine, there is an urgent need to understand and identify key factors involved in the biology of metastasis, to predict gastric cancer outcome, but PRL-3 (phosphatase of regenerating liver-3, known as PTP4A3) belongs to the the family of protein tyrosine phosphatases (PTPs). Afterwards, Wang et al found that overexpression of PRL-3 was present in 47.7% of gastric carcinomas with the lymph node metastasis using monoclonal antibody [13] and reported its prognostic significance [13]. Correlation between PRL-3 overexpression and lymph node metastasis or peritoneal metastasis has been reported at some aspects in gastric cancer [12,14], the identical expression in the primary tumors without metastasis, primary tumors with metastasis, and matched samples of primary lesion and liver metastasis has not been completely understood. We examined the clinical significance of PRL-3 in gastric cancer together with its metastatic biological functions utilizing different structural mutants
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
