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PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma

BACKGROUND: 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 sig...

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Autores principales: Saukkonen, Kapo, Hagström, Jaana, Mustonen, Harri, Juuti, Anne, Nordling, Stig, Kallio, Pauliina, Alitalo, Kari, Seppänen, Hanna, Haglund, Caj
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944261/
https://www.ncbi.nlm.nih.gov/pubmed/27411302
http://dx.doi.org/10.1186/s12885-016-2497-5
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author Saukkonen, Kapo
Hagström, Jaana
Mustonen, Harri
Juuti, Anne
Nordling, Stig
Kallio, Pauliina
Alitalo, Kari
Seppänen, Hanna
Haglund, Caj
author_facet Saukkonen, Kapo
Hagström, Jaana
Mustonen, Harri
Juuti, Anne
Nordling, Stig
Kallio, Pauliina
Alitalo, Kari
Seppänen, Hanna
Haglund, Caj
author_sort Saukkonen, Kapo
collection PubMed
description BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: In conclusion, high PROX1 and β-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2497-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-49442612016-07-15 PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma Saukkonen, Kapo Hagström, Jaana Mustonen, Harri Juuti, Anne Nordling, Stig Kallio, Pauliina Alitalo, Kari Seppänen, Hanna Haglund, Caj BMC Cancer Research Article BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSION: In conclusion, high PROX1 and β-catenin expression were independent factors for better prognosis in pancreatic ductal adenocarcinoma. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2497-5) contains supplementary material, which is available to authorized users. BioMed Central 2016-07-13 /pmc/articles/PMC4944261/ /pubmed/27411302 http://dx.doi.org/10.1186/s12885-016-2497-5 Text en © The Author(s). 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Saukkonen, Kapo
Hagström, Jaana
Mustonen, Harri
Juuti, Anne
Nordling, Stig
Kallio, Pauliina
Alitalo, Kari
Seppänen, Hanna
Haglund, Caj
PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
title PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
title_full PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
title_fullStr PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
title_full_unstemmed PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
title_short PROX1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
title_sort prox1 and β-catenin are prognostic markers in pancreatic ductal adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4944261/
https://www.ncbi.nlm.nih.gov/pubmed/27411302
http://dx.doi.org/10.1186/s12885-016-2497-5
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