Cargando…

Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma

Dickkopf-2 (DKK2) has been described as Wnt/beta-catenin pathway antagonist and its expression is mediated by micro RNA-221 (miRNA-221). So far, there is only limited data characterizing the role of DKK2 expression in esophageal cancer. A tissue micro array of 192 patients with esophageal adenocarci...

Descripción completa

Detalles Bibliográficos
Autores principales: Schiffmann, Lars M., Loeser, Heike, Jacob, Anne Sophie, Maus, Martin, Fuchs, Hans, Zhao, Yue, Tharun, Lars, Essakly, Ahlem, Iannos Damanakis, Alexander, Zander, Thomas, Büttner, Reinhard, Schröder, Wolfgang, Bruns, Christiane, Quaas, Alexander, Gebauer, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072714/
https://www.ncbi.nlm.nih.gov/pubmed/32075129
http://dx.doi.org/10.3390/cancers12020451
_version_ 1783506470859440128
author Schiffmann, Lars M.
Loeser, Heike
Jacob, Anne Sophie
Maus, Martin
Fuchs, Hans
Zhao, Yue
Tharun, Lars
Essakly, Ahlem
Iannos Damanakis, Alexander
Zander, Thomas
Büttner, Reinhard
Schröder, Wolfgang
Bruns, Christiane
Quaas, Alexander
Gebauer, Florian
author_facet Schiffmann, Lars M.
Loeser, Heike
Jacob, Anne Sophie
Maus, Martin
Fuchs, Hans
Zhao, Yue
Tharun, Lars
Essakly, Ahlem
Iannos Damanakis, Alexander
Zander, Thomas
Büttner, Reinhard
Schröder, Wolfgang
Bruns, Christiane
Quaas, Alexander
Gebauer, Florian
author_sort Schiffmann, Lars M.
collection PubMed
description Dickkopf-2 (DKK2) has been described as Wnt/beta-catenin pathway antagonist and its expression is mediated by micro RNA-221 (miRNA-221). So far, there is only limited data characterizing the role of DKK2 expression in esophageal cancer. A tissue micro array of 192 patients with esophageal adenocarcinoma was analyzed immunohistochemically for DKK2, miRNA-221 expression by RNA scope, and GATA6 amplification by fluorescence in-situ hybridization. The data was correlated with clinical, pathological and molecular data (TP53, HER2, c-myc, GATA6, PIK3CA, and KRAS amplifications). DKK2 expression was detectable in 21.7% and miRNA-221 expression in 33.5% of the patients. We observed no correlation between DKK2 or miRNA-221 expression and clinico-pathological data DKK2 expression was correlated with TP53 mutations and amplification of GATA6. We did not detect a survival difference in dependence of DKK2 for the total cohort, however, in patients without neoadjuvant treatment DKK2 expression correlated with a prolonged survival (median overall-survival 202 vs. 55 months, p = 0.012) which turned opposite in patients that underwent neoadjuvant treatment. High amounts of miRNA-221 were in trend associated with a prolonged overall-survival (p = 0.070). DKK2 as a Wnt antagonist is associated with prolonged survival in patients without neoadjuvant treatment and changes its prognostic value to the contrary in patients after neoadjuvant therapy. The modulatory effects of neoadjuvant treatment in connection with DKK2 expression are not fully understood, but when considering DKK2 as a tumor marker, it is necessary to see it in the context of neoadjuvant therapy.
format Online
Article
Text
id pubmed-7072714
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70727142020-03-19 Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma Schiffmann, Lars M. Loeser, Heike Jacob, Anne Sophie Maus, Martin Fuchs, Hans Zhao, Yue Tharun, Lars Essakly, Ahlem Iannos Damanakis, Alexander Zander, Thomas Büttner, Reinhard Schröder, Wolfgang Bruns, Christiane Quaas, Alexander Gebauer, Florian Cancers (Basel) Article Dickkopf-2 (DKK2) has been described as Wnt/beta-catenin pathway antagonist and its expression is mediated by micro RNA-221 (miRNA-221). So far, there is only limited data characterizing the role of DKK2 expression in esophageal cancer. A tissue micro array of 192 patients with esophageal adenocarcinoma was analyzed immunohistochemically for DKK2, miRNA-221 expression by RNA scope, and GATA6 amplification by fluorescence in-situ hybridization. The data was correlated with clinical, pathological and molecular data (TP53, HER2, c-myc, GATA6, PIK3CA, and KRAS amplifications). DKK2 expression was detectable in 21.7% and miRNA-221 expression in 33.5% of the patients. We observed no correlation between DKK2 or miRNA-221 expression and clinico-pathological data DKK2 expression was correlated with TP53 mutations and amplification of GATA6. We did not detect a survival difference in dependence of DKK2 for the total cohort, however, in patients without neoadjuvant treatment DKK2 expression correlated with a prolonged survival (median overall-survival 202 vs. 55 months, p = 0.012) which turned opposite in patients that underwent neoadjuvant treatment. High amounts of miRNA-221 were in trend associated with a prolonged overall-survival (p = 0.070). DKK2 as a Wnt antagonist is associated with prolonged survival in patients without neoadjuvant treatment and changes its prognostic value to the contrary in patients after neoadjuvant therapy. The modulatory effects of neoadjuvant treatment in connection with DKK2 expression are not fully understood, but when considering DKK2 as a tumor marker, it is necessary to see it in the context of neoadjuvant therapy. MDPI 2020-02-14 /pmc/articles/PMC7072714/ /pubmed/32075129 http://dx.doi.org/10.3390/cancers12020451 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schiffmann, Lars M.
Loeser, Heike
Jacob, Anne Sophie
Maus, Martin
Fuchs, Hans
Zhao, Yue
Tharun, Lars
Essakly, Ahlem
Iannos Damanakis, Alexander
Zander, Thomas
Büttner, Reinhard
Schröder, Wolfgang
Bruns, Christiane
Quaas, Alexander
Gebauer, Florian
Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma
title Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma
title_full Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma
title_fullStr Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma
title_full_unstemmed Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma
title_short Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma
title_sort dickkopf-2 (dkk2) as context dependent factor in patients with esophageal adenocarcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072714/
https://www.ncbi.nlm.nih.gov/pubmed/32075129
http://dx.doi.org/10.3390/cancers12020451
work_keys_str_mv AT schiffmannlarsm dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT loeserheike dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT jacobannesophie dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT mausmartin dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT fuchshans dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT zhaoyue dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT tharunlars dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT essaklyahlem dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT iannosdamanakisalexander dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT zanderthomas dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT buttnerreinhard dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT schroderwolfgang dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT brunschristiane dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT quaasalexander dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma
AT gebauerflorian dickkopf2dkk2ascontextdependentfactorinpatientswithesophagealadenocarcinoma