title: Low-Molecular-Weight Protein Tyrosine Phosphatase Predicts Prostate Cancer Outcome by Increasing the Metastatic Potential.
abstract: BACKGROUND
  Low-risk patients suffering from prostate cancer (PCa) are currently placed under active surveillance rather than undergoing radical prostatectomy. However, clear parameters for selecting the right patient for each strategy are not available, and new biomarkers and treatment modalities are needed. Low-molecular-weight protein tyrosine phosphatase (LMWPTP) could present such a target.
  
  
  OBJECTIVE
  To correlate expression levels of LMWPTP in primary PCa to clinical outcome, and determine the role of LMWPTP in prostate tumor cell biology.
  
  
  METHODS
  Acid phosphatase 1, soluble (ACP1) expression was analyzed on microarray data sets, which were subsequently used in Ingenuity Pathway Analysis. Immunohistochemistry was performed on a tissue microarray containing material of 481 PCa patients whose clinicopathologic data were recorded. PCa cell line models were used to investigate the role of LMWPTP in cell proliferation, migration, adhesion, and anoikis resistance.
  
  
  METHODS
  The association between LMWPTP expression and clinical and pathologic outcomes was calculated using chi-square correlations and multivariable Cox regression analysis. Functional consequences of LMWPTP overexpression or downregulation were determined using migration and adhesion assays, confocal microscopy, Western blotting, and proliferation assays.
  
  
  CONCLUSIONS
  LMWPTP expression was significantly increased in human PCa and correlated with earlier recurrence of disease (hazard ratio [HR]:1.99; p<0.001) and reduced patient survival (HR: 1.53; p=0.04). Unbiased Ingenuity analysis comparing cancer and normal prostate suggests migratory propensities in PCa. Indeed, overexpression of LMWPTP increases PCa cell migration, anoikis resistance, and reduces activation of focal adhesion kinase/paxillin, corresponding to decreased adherence.
  
  
  CONCLUSIONS
  Overexpression of LMWPTP in PCa confers a malignant phenotype with worse clinical outcome. Prospective follow-up should determine the clinical potential of LMWPTP overexpression.
  
  
  RESULTS
  These findings implicate low-molecular-weight protein tyrosine phosphatase as a novel oncogene in prostate cancer and could offer the possibility of using this protein as biomarker or target for treatment of this disease.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands; Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
authors.forename: Roberta R
authors.initials: RR
authors.lastname: Ruela-de-Sousa
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Elmer
authors.initials: E
authors.lastname: Hoekstra
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: A Marije
authors.initials: AM
authors.lastname: Hoogland
authors.affiliation: Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil; Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Karla C
authors.initials: KC
authors.lastname: Souza Queiroz
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.affiliation: Department of Bioinformatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Stubbs
authors.affiliation: Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
authors.forename: Karin
authors.initials: K
authors.lastname: Pelizzaro-Rocha
authors.affiliation: Department of Pathology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Geert J L H
authors.initials: GJLH
authors.lastname: van Leenders
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Guido
authors.initials: G
authors.lastname: Jenster
authors.affiliation: Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.affiliation: Department of Biochemistry and Tissue Biology, University of Campinas, Campinas, Brazil.
authors.forename: Carmen V
authors.initials: CV
authors.lastname: Ferreira
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: g.fuhler@erasmusmc.nl.
authors.forename: Gwenny M
authors.initials: GM
authors.lastname: Fuhler
mesh_terms: D000368:Aged; D023102:Anoikis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D018579:Patient Selection; D051419:Paxillin / Q000378:metabolism; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D046888:Tissue Array Analysis; D014162:Transfection; D015854:Up-Regulation; D057832:Watchful Waiting
chemical_list: D014408:Biomarkers, Tumor; C496061:PXN protein, human; D051419:Paxillin; D011518:Proto-Oncogene Proteins; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C490429:ACP1 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: Biomarker; Metastasis; Phosphatases; Prostate cancer