Schiffmann, Lars M., Loeser, Heike ORCID: 0000-0003-4555-1327, Jacob, Anne Sophie, Maus, Martin, Fuchs, Hans, Zhao, Yue, Tharun, Lars, Essakly, Ahlem, Damanakis, Alexander Iannos, Zander, Thomas, Buettner, Reinhard, Schroeder, Wolfgang, Bruns, Christiane, Quaas, Alexander and Gebauer, Florian (2020). Dickkopf-2 (DKK2) as Context Dependent Factor in Patients with Esophageal Adenocarcinoma. Cancers, 12 (2). BASEL: MDPI. ISSN 2072-6694

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Abstract

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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schiffmann, Lars M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Loeser, HeikeUNSPECIFIEDorcid.org/0000-0003-4555-1327UNSPECIFIED
Jacob, Anne SophieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Maus, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fuchs, HansUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zhao, YueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tharun, LarsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Essakly, AhlemUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Damanakis, Alexander IannosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zander, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Buettner, ReinhardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schroeder, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bruns, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Quaas, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gebauer, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-346061
DOI: 10.3390/cancers12020451
Journal or Publication Title: Cancers
Volume: 12
Number: 2
Date: 2020
Publisher: MDPI
Place of Publication: BASEL
ISSN: 2072-6694
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CANCER; PATHWAY; SURGERY; BETAMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/34606

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