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Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma

BACKGROUND: Molecular markers predicting survival in esophageal adenocarcinoma (EAC) are rare. Specifically, in favorable oncologic situations, e.g. nodal negativity or major neoadjuvant therapy response, there is a lack of additional risk factors that serve to predict patients’ outcome more precise...

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Autores principales: Schiffmann, Lars M., Göbel, Heike, Löser, Heike, Schorn, Fabian, Werthenbach, Jan Paul, Fuchs, Hans F., Plum, Patrick S., Bludau, Marc, Zander, Thomas, Schröder, Wolfgang, Bruns, Christiane J., Kashkar, Hamid, Quaas, Alexander, Gebauer, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545033/
https://www.ncbi.nlm.nih.gov/pubmed/31151416
http://dx.doi.org/10.1186/s12885-019-5722-1
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author Schiffmann, Lars M.
Göbel, Heike
Löser, Heike
Schorn, Fabian
Werthenbach, Jan Paul
Fuchs, Hans F.
Plum, Patrick S.
Bludau, Marc
Zander, Thomas
Schröder, Wolfgang
Bruns, Christiane J.
Kashkar, Hamid
Quaas, Alexander
Gebauer, Florian
author_facet Schiffmann, Lars M.
Göbel, Heike
Löser, Heike
Schorn, Fabian
Werthenbach, Jan Paul
Fuchs, Hans F.
Plum, Patrick S.
Bludau, Marc
Zander, Thomas
Schröder, Wolfgang
Bruns, Christiane J.
Kashkar, Hamid
Quaas, Alexander
Gebauer, Florian
author_sort Schiffmann, Lars M.
collection PubMed
description BACKGROUND: Molecular markers predicting survival in esophageal adenocarcinoma (EAC) are rare. Specifically, in favorable oncologic situations, e.g. nodal negativity or major neoadjuvant therapy response, there is a lack of additional risk factors that serve to predict patients’ outcome more precisely. This study evaluated X-linked inhibitor of apoptosis protein (XIAP) as a potential marker improving outcome prediction. METHODS: Tissue microarrays from 362 patients that were diagnosed with resectable EAC were included in the study. XIAP was stained by immunohistochemistry and correlated to clinical outcome, molecular markers and markers of the cellular tumor microenvironment. RESULTS: XIAP did not impact on overall survival (OS) in the whole study collective. Subgroup analyses stratifying for common genetic markers (TP53, ERBB2, ARID1A/SWI/SNF) did not disclose any impact of XIAP expression on survival. Detailed subgroup analyses of [1] nodal negative patients, [2] highly T-cell infiltrated tumors and [3] therapy responders to neoadjuvant treatment revealed a significant inverse role of high XIAP expression in these specific oncologic situations; elevated XIAP expression detrimentally affected patients’ outcome in these subgroups. [1]: OS XIAP low: 202 months (m) vs. XIAP high: 38 m; [2]: OS 116 m vs. 28.2 m; [3]: OS 31 m vs. 4 m). CONCLUSIONS: Our data suggest XIAP expression in EAC as a worthy tool to improve outcome prediction in specific oncologic settings that might directly impact on clinical diagnosis and treatment of EAC in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5722-1) contains supplementary material, which is available to authorized users.
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spelling pubmed-65450332019-06-04 Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma Schiffmann, Lars M. Göbel, Heike Löser, Heike Schorn, Fabian Werthenbach, Jan Paul Fuchs, Hans F. Plum, Patrick S. Bludau, Marc Zander, Thomas Schröder, Wolfgang Bruns, Christiane J. Kashkar, Hamid Quaas, Alexander Gebauer, Florian BMC Cancer Research Article BACKGROUND: Molecular markers predicting survival in esophageal adenocarcinoma (EAC) are rare. Specifically, in favorable oncologic situations, e.g. nodal negativity or major neoadjuvant therapy response, there is a lack of additional risk factors that serve to predict patients’ outcome more precisely. This study evaluated X-linked inhibitor of apoptosis protein (XIAP) as a potential marker improving outcome prediction. METHODS: Tissue microarrays from 362 patients that were diagnosed with resectable EAC were included in the study. XIAP was stained by immunohistochemistry and correlated to clinical outcome, molecular markers and markers of the cellular tumor microenvironment. RESULTS: XIAP did not impact on overall survival (OS) in the whole study collective. Subgroup analyses stratifying for common genetic markers (TP53, ERBB2, ARID1A/SWI/SNF) did not disclose any impact of XIAP expression on survival. Detailed subgroup analyses of [1] nodal negative patients, [2] highly T-cell infiltrated tumors and [3] therapy responders to neoadjuvant treatment revealed a significant inverse role of high XIAP expression in these specific oncologic situations; elevated XIAP expression detrimentally affected patients’ outcome in these subgroups. [1]: OS XIAP low: 202 months (m) vs. XIAP high: 38 m; [2]: OS 116 m vs. 28.2 m; [3]: OS 31 m vs. 4 m). CONCLUSIONS: Our data suggest XIAP expression in EAC as a worthy tool to improve outcome prediction in specific oncologic settings that might directly impact on clinical diagnosis and treatment of EAC in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-019-5722-1) contains supplementary material, which is available to authorized users. BioMed Central 2019-05-31 /pmc/articles/PMC6545033/ /pubmed/31151416 http://dx.doi.org/10.1186/s12885-019-5722-1 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Schiffmann, Lars M.
Göbel, Heike
Löser, Heike
Schorn, Fabian
Werthenbach, Jan Paul
Fuchs, Hans F.
Plum, Patrick S.
Bludau, Marc
Zander, Thomas
Schröder, Wolfgang
Bruns, Christiane J.
Kashkar, Hamid
Quaas, Alexander
Gebauer, Florian
Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
title Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
title_full Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
title_fullStr Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
title_full_unstemmed Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
title_short Elevated X-linked inhibitor of apoptosis protein (XIAP) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and T-cell rich esophageal adenocarcinoma
title_sort elevated x-linked inhibitor of apoptosis protein (xiap) expression uncovers detrimental prognosis in subgroups of neoadjuvant treated and t-cell rich esophageal adenocarcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545033/
https://www.ncbi.nlm.nih.gov/pubmed/31151416
http://dx.doi.org/10.1186/s12885-019-5722-1
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