Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.

A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Julia Slotta-Huspenina, Daniela Berg, Karina Bauer, Claudia Wolff, Katharina Malinowsky, Lukas Bauer, Enken Drecoll, Marcus Bettstetter, Marcus Feith, Axel Walch, Heinz Höfler, Karl-Friedrich Becker, Rupert Langer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4aae40a50cdc46259460727e6d872eb3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4aae40a50cdc46259460727e6d872eb3
record_format	dspace
spelling	oai:doaj.org-article:4aae40a50cdc46259460727e6d872eb32021-11-18T07:11:18ZEvidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.1932-620310.1371/journal.pone.0041420https://doaj.org/article/4aae40a50cdc46259460727e6d872eb32012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22911792/?tool=EBIhttps://doaj.org/toc/1932-6203A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27((Ser15)), p-HSP27((Ser78)), p-HSP27((Ser82)), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82)) and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.Julia Slotta-HuspeninaDaniela BergKarina BauerClaudia WolffKatharina MalinowskyLukas BauerEnken DrecollMarcus BettstetterMarcus FeithAxel WalchHeinz HöflerKarl-Friedrich BeckerRupert LangerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 7, p e41420 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Julia Slotta-Huspenina Daniela Berg Karina Bauer Claudia Wolff Katharina Malinowsky Lukas Bauer Enken Drecoll Marcus Bettstetter Marcus Feith Axel Walch Heinz Höfler Karl-Friedrich Becker Rupert Langer Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
description	A high percentage of oesophageal adenocarcinomas show an aggressive clinical behaviour with a significant resistance to chemotherapy. Heat-shock proteins (HSPs) and glucose-regulated proteins (GRPs) are molecular chaperones that play an important role in tumour biology. Recently, novel therapeutic approaches targeting HSP90/GRP94 have been introduced for treating cancer. We performed a comprehensive investigation of HSP and GRP expression including HSP27, phosphorylated (p)-HSP27((Ser15)), p-HSP27((Ser78)), p-HSP27((Ser82)), HSP60, HSP70, HSP90, GRP78 and GRP94 in 92 primary resected oesophageal adenocarcinomas by using reverse phase protein arrays (RPPA), immunohistochemistry (IHC) and real-time quantitative RT-PCR (qPCR). Results were correlated with pathologic features and survival. HSP/GRP protein and mRNA expression was detected in all tumours at various levels. Unsupervised hierarchical clustering showed two distinct groups of tumours with specific protein expression patterns: The hallmark of the first group was a high expression of p-HSP27((Ser15, Ser78, Ser82)) and low expression of GRP78, GRP94 and HSP60. The second group showed the inverse pattern with low p-HSP27 and high GRP78, GRP94 and HSP60 expression. The clinical outcome for patients from the first group was significantly improved compared to patients from the second group, both in univariate analysis (p = 0.015) and multivariate analysis (p = 0.029). Interestingly, these two groups could not be distinguished by immunohistochemistry or qPCR analysis. In summary, two distinct and prognostic relevant HSP/GRP protein expression patterns in adenocarcinomas of the oesophagus were detected by RPPA. Our approach may be helpful for identifying candidates for specific HSP/GRP-targeted therapies.
format	article
author	Julia Slotta-Huspenina Daniela Berg Karina Bauer Claudia Wolff Katharina Malinowsky Lukas Bauer Enken Drecoll Marcus Bettstetter Marcus Feith Axel Walch Heinz Höfler Karl-Friedrich Becker Rupert Langer
author_facet	Julia Slotta-Huspenina Daniela Berg Karina Bauer Claudia Wolff Katharina Malinowsky Lukas Bauer Enken Drecoll Marcus Bettstetter Marcus Feith Axel Walch Heinz Höfler Karl-Friedrich Becker Rupert Langer
author_sort	Julia Slotta-Huspenina
title	Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
title_short	Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
title_full	Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
title_fullStr	Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
title_full_unstemmed	Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
title_sort	evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/4aae40a50cdc46259460727e6d872eb3
work_keys_str_mv	AT juliaslottahuspenina evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT danielaberg evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT karinabauer evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT claudiawolff evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT katharinamalinowsky evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT lukasbauer evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT enkendrecoll evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT marcusbettstetter evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT marcusfeith evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT axelwalch evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT heinzhofler evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT karlfriedrichbecker evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas AT rupertlanger evidenceofprognosticrelevantexpressionprofilesofheatshockproteinsandglucoseregulatedproteinsinoesophagealadenocarcinomas
_version_	1718423783950254080

Evidence of prognostic relevant expression profiles of heat-shock proteins and glucose-regulated proteins in oesophageal adenocarcinomas.

Ejemplares similares