Abstract
Background
The purposes of the current study were to investigate whether overexpression of the PRL-1 is clinically relevant to hepatocellular carcinoma (HCC) and whether expression patterns of PRL-1 in HCC have diagnostic and prognostic value.
Methods
Immunohistochemistry analysis was performed for PRL-1 in 60 HCC samples. The data were correlated with clinicopathological features. The univariate and multivariate survival analyses were also performed to determine their prognostic significance.
Results
PRL-1 protein was overexpressed (83%) in HCC as compared with the adjacent normal tissue. PRL-1 expression was not influenced by chronic alcohol exposure or cirrhosis. High expression of PRL-1 was correlated with smoking (p=0.012), cirrhosis (p=0.047) and histological grade (p=0.055). The Kaplan-Meier survival curves showed that high PRL-1 expression related to a poor survival with statistical significance (I vs. III, p=0.010; II vs. III, p=0.001). Univariate analysis showed that PRL-1 expression was associated with tumour size, stage and PRL-1 score. Multivariate analysis revealed that the PRL-1 protein expression level was an independent factor for overall survival (HR, 5.367; 95% CI, 2.270–12.692; p=0.001). This is the first demonstration that the expression level of PRL-1 is correlated with tumour progression and prognosis in HCC.
Conclusions
Along with other results, the PRL-1 protein is a candidate biomarker and a potential target for novel therapies against human HCC progression.
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References
WHO (2003) The World Health Report 2003: shaping the future. World Health Organization, Geneva, pp 1–11
Bosch FX, Ribes J, Diaz M et al (2004) Primary liver cancer: worldwide incidence and trends. Gastroenterology 127:S5–S16
Llovet JM, Beaugrand M (2003) Hepatocellular carcinoma: present status and future prospects. J Hepatol 38[Suppl 1]:S136–149
Nagao Y, Tanaka K, Kobayashi K et al (2004) A cohort study of chronic liver disease in an HCV hyperendemic area of Japan: a prospective analysis for 12 years. Int J Mol Med 13:257–265
Van Rensburg SJ, Cook-Mozaffari P, Van Schalkwyk DJ et al (1985) Hepatocellular carcinoma and dietary aflatoxin in Mozambique and Transkei. Br J Cancer 51:713–726
Beasley RP, Hwang LY, Lin CC et al (1981) Hepatocellular carcinoma and hepatitis B virus. A prospective study of 22 707 men in Taiwan. Lancet 2:1129–1133
Bessette DC, Qiu D, Pallen CJ (2008) PRL PTPs: mediators and markers of cancer progression. Cancer Metastasis Rev 27:231–252
Matter WF, Estridge T, Zhang C et al (2001) Role of PRL-3, a human muscle-specific tyrosine phosphatase, in angiotensin-II signaling. Biochem Biophys Res Commun 283:1061–1068
Dumaual CM, Sandusky GE, Crowell PL et al (2006) Cellular localization of PRL-1 and PRL-2 gene expression in normal adult human tissues. J Histochem Cytochem 54:1401–1412
Al-Aidaroos AQ, Zeng Q, Polato F et al (2010) PRL-3 phosphatase and cancer metastasis. J Cell Biochem 111:1087–1098
Kato H, Semba S, Miskad UA et al (2004) High expression of PRL-3 promotes cancer cell motility and liver metastasis in human colorectal cancer: a predictive molecular marker of metachronous liver and lung metastases. Clin Cancer Res 10:7318–7328
Liang F, Liang J, Wang WQ et al (2007) PRL3 promotes cell invasion and proliferation by downregulation of Csk leading to Src activation. J Biol Chem 282:5413–5419
Polato F, Codegoni A, Fruscio R et al (2005) PRL-3 phosphatase is implicated in ovarian cancer growth. Clin Cancer Res 11:6835–6839
Zhao WB, Li Y, Liu X et al (2008) Evaluation of PRL-3 expression, and its correlation with angiogenesis and invasion in hepatocellular carcinoma. Int J Mol Med 22:187–192
Radke I, Gotte M, Kersting C et al (2006) Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer. Br J Cancer 95:347–354
Bardelli A, Saha S, Sager JA et al (2003) PRL-3 expression in metastatic cancers. Clin Cancer Res 9:5607–5615
Diamond RH, Cressman DE, Laz TM et al (1994) PRL-1, a unique nuclear protein tyrosine phosphatase, affects cell growth. Mol Cell Biol 14: 3752–3762
Li J, Guo K, Koh VW et al (2005) Generation of PRL-3- and PRL-1-specific monoclonal antibodies as potential diagnostic markers for cancer metastases. Clin Cancer Res 11:2195–2204
Zeng Q, Dong JM, Guo K et al (2003) PRL-3 and PRL-1 promote cell migration, invasion, and metastasis. Cancer Res 63:2716–2722
Liu YQ, Li HX, Lou X et al (2008) Expression of phosphatase of regenerating liver 1 and 3 mRNA in esophageal squamous cell carcinoma. Arch Pathol Lab Med 132:1307–1312
Xu XR, Huang J, Xu ZG et al (2001) Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. Proc Natl Acad Sci U S A 98:15089–15094
Chen X, Cheung ST, So S et al (2002) Gene expression patterns in human liver cancers. Mol Biol Cell 13:1929–1939
Su WH, Chao CC, Yeh SH et al (2007) OncoDB. HCC: an integrated oncogenomic database of hepatocellular carcinoma revealed aberrant cancer target genes and loci. Nucleic Acids Res 35:D727–731
Hirohashi SK, Kojiro M, Puig PL et al (2000) Hepatocellular carcinoma. In: Hamilton SR, Aaltonen LA (eds) Pathology and genetics of tumours of the digestive system. IARC Press, Lyon, pp 159–172
Greene FL, Page DL, Fleming ID et al (eds) (2002) Digestive system. In: AJCC Cancer Staging Manual, 6th edn. Springer, New York, pp 131–136
Chang YS, Yeh KT, Yang MY et al (2005) Abnormal expression of JUNB gene in hepatocellular carcinoma. Oncol Rep 13:433–438
Lu JW, Chang JG, Yeh KT et al (2011) Decreased expression of p39 is associated with a poor prognosis in human hepatocellular carcinoma. Med Oncol 28[Suppl 1]:239–245
Lu JW, Chang JG, Yeh KT et al (2011) Overexpression of Thy1/CD90 in human hepatocellular carcinoma is associated with HBV infection and poor prognosis. Acta Histochem 113:833–838
Mantel N (1966) Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 50:163–170
Sun JP, Wang WQ, Yang H et al (2005) Structure and biochemical properties of PRL-1, a phosphatase implicated in cell growth, differentiation, and tumor invasion. Biochemistry 44:12009–12021
Zeng Q, Si X, Horstmann H et al (2000) Prenylation-dependent association of protein-tyrosine phosphatases PRL-1, -2, and -3 with the plasma membrane and the early endosome. J Biol Chem 275:21444–21452
Diamond RH, Peters C, Jung SP et al (1996) Expression of PRL-1 nuclear PTPase is associated with proliferation in liver but with differentiation in intestine. Am J Physiol 271:G121–129
Wang Q, Holmes DI, Powell SM et al (2002) Analysis of stromal-epithelial interactions in prostate cancer identifies PTPCAAX2 as a potential oncogene. Cancer Lett 175:63–69
Kong W, Swain GP, Li S et al (2000) PRL-1 PTPase expression is developmentally regulated with tissue-specific patterns in epithelial tissues Am J Physiol Gastrointest Liver Physiol 279:G613–621
Peng Y, Du K, Ramirez S et al (1999) Mitogenic up-regulation of the PRL-1 protein-tyrosine phosphatase gene by Egr-1. Egr-1 activation is an early event in liver regeneration. J Biol Chem 274:4513–4520
Luo Y, Liang F, Zhang ZY (2009) PRL1 promotes cell migration and invasion by increasing MMP2 and MMP9 expression through Src and ERK1/2 pathways. Biochemistry 48:1838–1846
Sun JP, Luo Y, Yu X et al (2007) Phosphatase activity, trimerization, and the C-terminal polybasic region are all required for PRL1-mediated cell growth and migration. J Biol Chem 282:29043–29051
Werner SR, Lee PA, DeCamp MW et al (2003) Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases. Cancer Lett 202:201–211
Min SH, Kim DM, Heo YS et al (2009) New p53 target, phosphatase of regenerating liver 1 (PRL-1) downregulates p53. Oncogene 28:545–554
Achiwa H, Lazo JS (2007) PRL-1 tyrosine phosphatase regulates c-Src levels, adherence, and invasion in human lung cancer cells. Cancer Res 67:643–650
Guo K, Tang JP, Tan CP et al (2008) Monoclonal antibodies target intracellular PRL phosphatases to inhibit cancer metastases in mice. Cancer Biol Ther 7:750–757
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Lu, JW., Chang, JG., Yeh, KT. et al. Increased expression of PRL-1 protein correlates with shortened patient survival in human hepatocellular carcinoma. Clin Transl Oncol 14, 287–293 (2012). https://doi.org/10.1007/s12094-012-0797-z
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DOI: https://doi.org/10.1007/s12094-012-0797-z