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Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer

The tumor necrosis factor–related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other member...

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Autores principales: Pombeiro, Ines, Loosen, Sven H., Roy, Sanchari, Schueller, Florian, Niewenhuisen, Lukas, Luedde, Mark, Vucur, Mihael, Tacke, Frank, Binnebösel, Marcel, Schoening, Wenzel, Trautwein, Christian, Luedde, Tom, Neumann, Ulf Peter, Roderburg, Christoph
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068811/
https://www.ncbi.nlm.nih.gov/pubmed/30011858
http://dx.doi.org/10.3390/jcm7070175
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author Pombeiro, Ines
Loosen, Sven H.
Roy, Sanchari
Schueller, Florian
Niewenhuisen, Lukas
Luedde, Mark
Vucur, Mihael
Tacke, Frank
Binnebösel, Marcel
Schoening, Wenzel
Trautwein, Christian
Luedde, Tom
Neumann, Ulf Peter
Roderburg, Christoph
author_facet Pombeiro, Ines
Loosen, Sven H.
Roy, Sanchari
Schueller, Florian
Niewenhuisen, Lukas
Luedde, Mark
Vucur, Mihael
Tacke, Frank
Binnebösel, Marcel
Schoening, Wenzel
Trautwein, Christian
Luedde, Tom
Neumann, Ulf Peter
Roderburg, Christoph
author_sort Pombeiro, Ines
collection PubMed
description The tumor necrosis factor–related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other members of the TNF ligand superfamily, its role as a biomarker in pancreatic cancer is currently unknown. We analyzed serum levels of A proliferation-inducing ligand (APRIL) and TWEAK in 134 patients with pancreatic cancer. Results were compared with 50 healthy controls and correlated with clinical data. Intratumoral expression of APRIL and TWEAK in pancreatic cancer was analysed using the datasets made available by the TCGA-LIHC project. APRIL serum levels were significantly elevated in patients with pancreatic cancer compared to healthy controls, which is in line with previous findings. Notably, the diagnostic accuracy of circulating APRIL levels was similar to CA19-9, an established tumor marker for pancreatic cancer. In contrast, serum concentrations of TWEAK were decreased in pancreatic cancer patients. Interestingly, no differences in TWEAK concentrations became apparent between different clinical subgroups of pancreatic cancer. Moreover, within our cohort of patients, TWEAK levels did not correlate with the patients’ prognosis and the diagnostic as well as prognostic potential of TWEAK was lower than CA 19-9, when analyzed in this setting. Finally, using data from the TCGA-LIHC project, we demonstrate that expression levels of TWEAK and APRIL represent prognostic markers for patients’ survival according to Kaplan-Meier curve analyses. TWEAK and APRIL serum concentrations are regulated differently in patients with pancreatic cancer, highlighting diverse roles of variant TNF ligands in this type of cancer.
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spelling pubmed-60688112018-08-07 Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer Pombeiro, Ines Loosen, Sven H. Roy, Sanchari Schueller, Florian Niewenhuisen, Lukas Luedde, Mark Vucur, Mihael Tacke, Frank Binnebösel, Marcel Schoening, Wenzel Trautwein, Christian Luedde, Tom Neumann, Ulf Peter Roderburg, Christoph J Clin Med Article The tumor necrosis factor–related weak inducer of apoptosis (TWEAK) belongs to the tumor necrosis factor ligand superfamily, which was shown to play an important role in inflammatory and malignant gastrointestinal diseases, including colitis or colorectal cancer. However, in contrast to other members of the TNF ligand superfamily, its role as a biomarker in pancreatic cancer is currently unknown. We analyzed serum levels of A proliferation-inducing ligand (APRIL) and TWEAK in 134 patients with pancreatic cancer. Results were compared with 50 healthy controls and correlated with clinical data. Intratumoral expression of APRIL and TWEAK in pancreatic cancer was analysed using the datasets made available by the TCGA-LIHC project. APRIL serum levels were significantly elevated in patients with pancreatic cancer compared to healthy controls, which is in line with previous findings. Notably, the diagnostic accuracy of circulating APRIL levels was similar to CA19-9, an established tumor marker for pancreatic cancer. In contrast, serum concentrations of TWEAK were decreased in pancreatic cancer patients. Interestingly, no differences in TWEAK concentrations became apparent between different clinical subgroups of pancreatic cancer. Moreover, within our cohort of patients, TWEAK levels did not correlate with the patients’ prognosis and the diagnostic as well as prognostic potential of TWEAK was lower than CA 19-9, when analyzed in this setting. Finally, using data from the TCGA-LIHC project, we demonstrate that expression levels of TWEAK and APRIL represent prognostic markers for patients’ survival according to Kaplan-Meier curve analyses. TWEAK and APRIL serum concentrations are regulated differently in patients with pancreatic cancer, highlighting diverse roles of variant TNF ligands in this type of cancer. MDPI 2018-07-13 /pmc/articles/PMC6068811/ /pubmed/30011858 http://dx.doi.org/10.3390/jcm7070175 Text en © 2018 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
Pombeiro, Ines
Loosen, Sven H.
Roy, Sanchari
Schueller, Florian
Niewenhuisen, Lukas
Luedde, Mark
Vucur, Mihael
Tacke, Frank
Binnebösel, Marcel
Schoening, Wenzel
Trautwein, Christian
Luedde, Tom
Neumann, Ulf Peter
Roderburg, Christoph
Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer
title Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer
title_full Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer
title_fullStr Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer
title_full_unstemmed Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer
title_short Differential Roles of Tumor Necrosis Factor Ligand Superfamily Members as Biomarkers in Pancreatic Cancer
title_sort differential roles of tumor necrosis factor ligand superfamily members as biomarkers in pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6068811/
https://www.ncbi.nlm.nih.gov/pubmed/30011858
http://dx.doi.org/10.3390/jcm7070175
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