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.
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.
Department of Hepato-Biliary-Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Abudureheman
A
Mayinuer
Mahmut
M
Yasen
Kaoru
K
Mogushi
Gulanbar
G
Obulhasim
Maimaiti
M
Xieraili
Arihiro
A
Aihara
Shinji
S
Tanaka
Hiroshi
H
Mizushima
Hiroshi
H
Tanaka
Shigeki
S
Arii
D015415:Biomarkers / Q000097:blood; D001808:Blood Vessels / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006509:Hepatitis B / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011498:Protein Precursors / Q000097:blood; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D011516:Prothrombin; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D000509:alpha-Fetoproteins / Q000378:metabolism
D015415:Biomarkers; D009363:Neoplasm Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D000509:alpha-Fetoproteins; C008208:acarboxyprothrombin; D011516:Prothrombin; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases