title: PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma.
abstract: The Wnt/β-catenin pathway has a key role in regulating cellular processes and its aberrant signaling can lead to cancer development. The role of β-catenin expression in pancreatic ductal adenocarcinoma is somewhat controversial. Transcription factor PROX1 is a target of Wnt/β-catenin signaling and it is involved in carcinogenesis through alterations in its expression. The actions can be either oncogenic or tumor suppressive depending on the tissue. The aim of this study was to investigate PROX1 and β-catenin expression in pancreatic ductal adenocarcinoma (PDAC).
  
  
  
  Expression of PROX1 and β-catenin were evaluated in 156 patients by immunohistochemistry of tissue microarrays. Associations between tumor marker expression and clinicopathological parameters were assessed by the Fischer's exact-test or the linear-by-linear association test. The Kaplan-Meier method and log-rank test were used for survival analysis. Uni- and multivariate survival analyses were carried out by the Cox regression proportional hazard model.
  
  
  
  High PROX1 expression was seen in 74 (48 %) tumors, and high β-catenin expression in 100 (65 %). High β-catenin expression was associated with lower tumor grade (p = 0.025). High PROX1 and β-catenin expression associated significantly with lower risk of death from PDAC in multivariate analysis (HR = 0.63; 95 % CI 0.42-0.95, p = 0.026; and HR = 0.54; 95 % CI 0.35-0.82, p = 0.004; respectively). The combined high expression of PROX1 and β-catenin also predicted lower risk of death from PDAC (HR = 0.46; 95 % CI 0.28-0.76, p = 0.002).
  
  
  
  In conclusion, high PROX1 and β-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma.
authors.affiliation: Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland. kapo.saukkonen@helsinki.fi.|Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, Helsinki, FIN-00014, Finland. kapo.saukkonen@helsinki.fi.
authors.forename: Kapo
authors.initials: K
authors.lastname: Saukkonen
authors.affiliation: Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, Helsinki, FIN-00014, Finland.|Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, FIN-00014, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Hagström
authors.affiliation: Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland.
authors.forename: Harri
authors.initials: H
authors.lastname: Mustonen
authors.affiliation: Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland.
authors.forename: Anne
authors.initials: A
authors.lastname: Juuti
authors.affiliation: Department of Pathology, Haartman Institute and HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, FIN-00014, Finland.
authors.forename: Stig
authors.initials: S
authors.lastname: Nordling
authors.affiliation: Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, Helsinki, FIN-00014, Finland.
authors.forename: Pauliina
authors.initials: P
authors.lastname: Kallio
authors.affiliation: Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, Helsinki, FIN-00014, Finland.
authors.forename: Kari
authors.initials: K
authors.lastname: Alitalo
authors.affiliation: Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Seppänen
authors.affiliation: Department of Surgery, University of Helsinki and Helsinki University Hospital, P.O. Box 440, FIN-00029 HUS, Helsinki, Finland.|Research Programs Unit, Translational Cancer Biology, University of Helsinki, P.O. Box 63, Helsinki, FIN-00014, Finland.
authors.forename: Caj
authors.initials: C
authors.lastname: Haglund
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D018398:Homeodomain Proteins; D025521:Tumor Suppressor Proteins; D051176:beta Catenin; D000098551:Prospero-Related Homeobox 1 Protein
keywords: Beta-catenin; PROX1; Pancreatic ductal adenocarcinoma; Prognosis