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

Autor:	Martin K. H. Maus, Heike Loeser, Ahlem Essakly, Reinhard Büttner, Florian Gebauer, Alexander Quaas, Alexander Damanakis, Lars Schiffmann, Lars Tharun, Wolfgang Schröder, Christiane J. Bruns, Yue Zhao, Hans F. Fuchs, Thomas Zander, Anne Sophie Jacob
Rok vydání:	2020
Předmět:	0301 basic medicine Oncology Cancer Research medicine.medical_specialty medicine.medical_treatment Context (language use) medicine.disease_cause lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine GATA6 Internal medicine medicine EAC Pathological Neoadjuvant therapy Tumor marker business.industry DKK2 Wnt signaling pathway Esophageal cancer lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease 030104 developmental biology 030220 oncology & carcinogenesis response prediction KRAS business
Zdroj:	Cancers Cancers, Vol 12, Iss 2, p 451 (2020) Volume 12 Issue 2
ISSN:	2072-6694
DOI:	10.3390/cancers12020451
Popis:	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.
Databáze:	OpenAIRE
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