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...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/2/451 |
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| author | Lars M. Schiffmann Heike Loeser Anne Sophie Jacob Martin Maus Hans Fuchs Yue Zhao Lars Tharun Ahlem Essakly Alexander Iannos Damanakis Thomas Zander Reinhard Büttner Wolfgang Schröder Christiane Bruns Alexander Quaas Florian Gebauer |
| author_facet | Lars M. Schiffmann Heike Loeser Anne Sophie Jacob Martin Maus Hans Fuchs Yue Zhao Lars Tharun Ahlem Essakly Alexander Iannos Damanakis Thomas Zander Reinhard Büttner Wolfgang Schröder Christiane Bruns Alexander Quaas Florian Gebauer |
| author_sort | Lars M. Schiffmann |
| collection | DOAJ |
| 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, <i>c-myc</i>, <i>GATA</i>6, <i>PIK3CA,</i> and <i>KRAS</i> 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 <i>GATA6</i>. 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, <i>p</i> = 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 (<i>p</i> = 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. |
| first_indexed | 2024-03-12T10:22:59Z |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T10:22:59Z |
| publishDate | 2020-02-01 |
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| series | Cancers |
| spelling | doaj.art-c5dddd37e1bd403bb98411a52dd8beef2023-09-02T10:01:17ZengMDPI AGCancers2072-66942020-02-0112245110.3390/cancers12020451cancers12020451Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal AdenocarcinomaLars M. Schiffmann0Heike Loeser1Anne Sophie Jacob2Martin Maus3Hans Fuchs4Yue Zhao5Lars Tharun6Ahlem Essakly7Alexander Iannos Damanakis8Thomas Zander9Reinhard Büttner10Wolfgang Schröder11Christiane Bruns12Alexander Quaas13Florian Gebauer14Department of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Pathology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Pathology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Pathology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Gastrointestinal Cancer Group Cologne (GCGC), University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Pathology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of Pathology, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDepartment of General, Visceral and Cancer Surgery, University of Cologne, Kerpener Strasse 62, 50937 Cologne, GermanyDickkopf-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, <i>c-myc</i>, <i>GATA</i>6, <i>PIK3CA,</i> and <i>KRAS</i> 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 <i>GATA6</i>. 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, <i>p</i> = 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 (<i>p</i> = 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.https://www.mdpi.com/2072-6694/12/2/451response predictiondkk2gata6eac |
| spellingShingle | Lars M. Schiffmann Heike Loeser Anne Sophie Jacob Martin Maus Hans Fuchs Yue Zhao Lars Tharun Ahlem Essakly Alexander Iannos Damanakis Thomas Zander Reinhard Büttner Wolfgang Schröder Christiane Bruns Alexander Quaas Florian Gebauer Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma Cancers response prediction dkk2 gata6 eac |
| 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 | response prediction dkk2 gata6 eac |
| url | https://www.mdpi.com/2072-6694/12/2/451 |
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