Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.

<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pa...

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Autores principales:	Felix Rückert, Gihan Dawelbait, Christof Winter, Arndt Hartmann, Axel Denz, Ole Ammerpohl, Michael Schroeder, Hans Konrad Schackert, Bence Sipos, Günter Klöppel, Holger Kalthoff, Hans-Detlev Saeger, Christian Pilarsky, Robert Grützmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5de7354ae67846d6b179a55b9bd0ac2a
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spelling	oai:doaj.org-article:5de7354ae67846d6b179a55b9bd0ac2a2021-11-18T06:35:53ZExamination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.1932-620310.1371/journal.pone.0012243https://doaj.org/article/5de7354ae67846d6b179a55b9bd0ac2a2010-08-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20808857/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction.<h4>Methodology/principal findings</h4>Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway.<h4>Conclusions/significance</h4>Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC.Felix RückertGihan DawelbaitChristof WinterArndt HartmannAxel DenzOle AmmerpohlMichael SchroederHans Konrad SchackertBence SiposGünter KlöppelHolger KalthoffHans-Detlev SaegerChristian PilarskyRobert GrützmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 8, p e12243 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Felix Rückert Gihan Dawelbait Christof Winter Arndt Hartmann Axel Denz Ole Ammerpohl Michael Schroeder Hans Konrad Schackert Bence Sipos Günter Klöppel Holger Kalthoff Hans-Detlev Saeger Christian Pilarsky Robert Grützmann Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
description	<h4>Background</h4>Pancreatic ductal adenocarcinoma (PDAC) remains an important cause of cancer death. Changes in apoptosis signaling in pancreatic cancer result in chemotherapy resistance and aggressive growth and metastasizing. The aim of this study was to characterize the apoptosis pathway in pancreatic cancer computationally by evaluation of experimental data from high-throughput technologies and public data bases. Therefore, gene expression analysis of microdissected pancreatic tumor tissue was implemented in a model of the apoptosis pathway obtained by computational protein interaction prediction.<h4>Methodology/principal findings</h4>Apoptosis pathway related genes were assembled from electronic databases. To assess expression of these genes we constructed a virtual subarray from a whole genome analysis from microdissected native tumor tissue. To obtain a model of the apoptosis pathway, interactions of members of the apoptosis pathway were analysed using public databases and computational prediction of protein interactions. Gene expression data were implemented in the apoptosis pathway model. 19 genes were found differentially expressed and 12 genes had an already known pathophysiological role in PDAC, such as Survivin/BIRC5, BNIP3 and TNF-R1. Furthermore we validated differential expression of IL1R2 and Livin/BIRC7 by RT-PCR and immunohistochemistry. Implementation of the gene expression data in the apoptosis pathway map suggested two higher level defects of the pathway at the level of cell death receptors and within the intrinsic signaling cascade consistent with references on apoptosis in PDAC. Protein interaction prediction further showed possible new interactions between the single pathway members, which demonstrate the complexity of the apoptosis pathway.<h4>Conclusions/significance</h4>Our data shows that by computational evaluation of public accessible data an acceptable virtual image of the apoptosis pathway might be given. By this approach we could identify two higher level defects of the apoptosis pathway in PDAC. We could further for the first time identify IL1R2 as possible candidate gene in PDAC.
format	article
author	Felix Rückert Gihan Dawelbait Christof Winter Arndt Hartmann Axel Denz Ole Ammerpohl Michael Schroeder Hans Konrad Schackert Bence Sipos Günter Klöppel Holger Kalthoff Hans-Detlev Saeger Christian Pilarsky Robert Grützmann
author_facet	Felix Rückert Gihan Dawelbait Christof Winter Arndt Hartmann Axel Denz Ole Ammerpohl Michael Schroeder Hans Konrad Schackert Bence Sipos Günter Klöppel Holger Kalthoff Hans-Detlev Saeger Christian Pilarsky Robert Grützmann
author_sort	Felix Rückert
title	Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
title_short	Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
title_full	Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
title_fullStr	Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
title_full_unstemmed	Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
title_sort	examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/5de7354ae67846d6b179a55b9bd0ac2a
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Examination of apoptosis signaling in pancreatic cancer by computational signal transduction analysis.

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