Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma

Abstract ATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously sugge...

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Autores principales: Lenka Cervenkova, Ondrej Vycital, Jan Bruha, Jachym Rosendorf, Richard Palek, Vaclav Liska, Ondrej Daum, Beatrice Mohelnikova-Duchonova, Pavel Soucek
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Publicado: Nature Portfolio 2019
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Acceso en línea:https://doaj.org/article/a28799568d2c4b808e2376b6dbec6361
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spelling oai:doaj.org-article:a28799568d2c4b808e2376b6dbec63612021-12-02T13:35:12ZProtein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma10.1038/s41598-019-56059-w2045-2322https://doaj.org/article/a28799568d2c4b808e2376b6dbec63612019-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-56059-whttps://doaj.org/toc/2045-2322Abstract ATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously suggested putative prognostic markers ABCC2 and SLC22A3 in pancreatic cancer patients. Protein localization and brush border staining intensity of ABCC2 and SLC22A3 was assessed in tumor tissue blocks of 65 pancreatic cancer patients and associated with clinical data and survival of patients with regard to therapy. Negative SLC22A3 brush border staining in pancreatic tumors significantly increased the risk of both disease progression and patient´s death in univariate analyses. Multivariate analyses confirmed the association of SLC22A3 expression with progression-free survival of patients. A subgroup analysis of patients treated with regimens based on nucleoside analogs suggested that patients with negative brush border staining or apical localization of SLC22A3 in tumor cells have worse overall survival. The combination of positive ABCC2 and negative SLC22A3 brush border staining predicted worst overall survival and patients with positive brush border staining of both proteins had best overall and progression-free survival. The present study shows for the first time that the protein presence and to some extent also localization of SLC22A3 significantly associate with prognosis of pancreatic cancer in both unstratified and chemotherapy-treated patients. The combination of ABCC2 and SLC22A3 brush border staining also needs further attention in this regard.Lenka CervenkovaOndrej VycitalJan BruhaJachym RosendorfRichard PalekVaclav LiskaOndrej DaumBeatrice Mohelnikova-DuchonovaPavel SoucekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Lenka Cervenkova
Ondrej Vycital
Jan Bruha
Jachym Rosendorf
Richard Palek
Vaclav Liska
Ondrej Daum
Beatrice Mohelnikova-Duchonova
Pavel Soucek
Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
description Abstract ATP-binding cassette (ABC) and solute carrier (SLC) transporters translocate diverse substances across cellular membranes and their deregulation may cause drug resistance of cancers. This study investigated significance of protein expression and cellular localization of the previously suggested putative prognostic markers ABCC2 and SLC22A3 in pancreatic cancer patients. Protein localization and brush border staining intensity of ABCC2 and SLC22A3 was assessed in tumor tissue blocks of 65 pancreatic cancer patients and associated with clinical data and survival of patients with regard to therapy. Negative SLC22A3 brush border staining in pancreatic tumors significantly increased the risk of both disease progression and patient´s death in univariate analyses. Multivariate analyses confirmed the association of SLC22A3 expression with progression-free survival of patients. A subgroup analysis of patients treated with regimens based on nucleoside analogs suggested that patients with negative brush border staining or apical localization of SLC22A3 in tumor cells have worse overall survival. The combination of positive ABCC2 and negative SLC22A3 brush border staining predicted worst overall survival and patients with positive brush border staining of both proteins had best overall and progression-free survival. The present study shows for the first time that the protein presence and to some extent also localization of SLC22A3 significantly associate with prognosis of pancreatic cancer in both unstratified and chemotherapy-treated patients. The combination of ABCC2 and SLC22A3 brush border staining also needs further attention in this regard.
format article
author Lenka Cervenkova
Ondrej Vycital
Jan Bruha
Jachym Rosendorf
Richard Palek
Vaclav Liska
Ondrej Daum
Beatrice Mohelnikova-Duchonova
Pavel Soucek
author_facet Lenka Cervenkova
Ondrej Vycital
Jan Bruha
Jachym Rosendorf
Richard Palek
Vaclav Liska
Ondrej Daum
Beatrice Mohelnikova-Duchonova
Pavel Soucek
author_sort Lenka Cervenkova
title Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
title_short Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
title_full Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
title_fullStr Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
title_full_unstemmed Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
title_sort protein expression of abcc2 and slc22a3 associates with prognosis of pancreatic adenocarcinoma
publisher Nature Portfolio
publishDate 2019
url https://doaj.org/article/a28799568d2c4b808e2376b6dbec6361
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