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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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 |
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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 |
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