Cargando…

A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma

BACKGROUND: The TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stag...

Descripción completa

Detalles Bibliográficos
Autores principales: Pasini, Fatima Solange, Zilberstein, Bruno, Snitcovsky, Igor, Roela, Rosimeire Aparecida, Mangone, Flavia R. Rotea, Ribeiro, Ulysses, Nonogaki, Suely, Brito, Glauber Costa, Callegari, Giovanna D., Cecconello, Ivan, Alves, Venancio Avancini Ferreira, Eluf-Neto, José, Chammas, Roger, Federico, Miriam Hatsue Honda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Japan 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223540/
https://www.ncbi.nlm.nih.gov/pubmed/24217965
http://dx.doi.org/10.1007/s00535-013-0904-0
_version_ 1782343213027164160
author Pasini, Fatima Solange
Zilberstein, Bruno
Snitcovsky, Igor
Roela, Rosimeire Aparecida
Mangone, Flavia R. Rotea
Ribeiro, Ulysses
Nonogaki, Suely
Brito, Glauber Costa
Callegari, Giovanna D.
Cecconello, Ivan
Alves, Venancio Avancini Ferreira
Eluf-Neto, José
Chammas, Roger
Federico, Miriam Hatsue Honda
author_facet Pasini, Fatima Solange
Zilberstein, Bruno
Snitcovsky, Igor
Roela, Rosimeire Aparecida
Mangone, Flavia R. Rotea
Ribeiro, Ulysses
Nonogaki, Suely
Brito, Glauber Costa
Callegari, Giovanna D.
Cecconello, Ivan
Alves, Venancio Avancini Ferreira
Eluf-Neto, José
Chammas, Roger
Federico, Miriam Hatsue Honda
author_sort Pasini, Fatima Solange
collection PubMed
description BACKGROUND: The TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets. METHODS: A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (<24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples. RESULTS: A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort. CONCLUSIONS: We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00535-013-0904-0) contains supplementary material, which is available to authorized users.
format Online
Article
Text
id pubmed-4223540
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Springer Japan
record_format MEDLINE/PubMed
spelling pubmed-42235402014-11-12 A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma Pasini, Fatima Solange Zilberstein, Bruno Snitcovsky, Igor Roela, Rosimeire Aparecida Mangone, Flavia R. Rotea Ribeiro, Ulysses Nonogaki, Suely Brito, Glauber Costa Callegari, Giovanna D. Cecconello, Ivan Alves, Venancio Avancini Ferreira Eluf-Neto, José Chammas, Roger Federico, Miriam Hatsue Honda J Gastroenterol Original Article—Alimentary Tract BACKGROUND: The TNM Classification of Malignant Tumours (TNM) staging system is the primary means of determining a prognosis for gastric adenocarcinoma (GC). However, tumor behavior in the individual patient is unpredictable and in spite of treatment advances, a classification of 'advanced stage' still portends a poor prognosis. Thus, further insights from molecular analyses are needed for better prognostic stratification and determination of new therapeutic targets. METHODS: A total of fifty-one fresh frozen tumor samples from patients with histopathologically confirmed diagnoses of GC, submitted to surgery with curative intent, were included in the study. Total RNA was extracted from an initial group of fifteen samples matched for known prognostic factors, categorized into two subgroups, according to patient overall survival: poor (<24 months) or favorable (at or above 24 months), and hybridized to Affymetrix Genechip human genome U133 plus 2.0 for genes associated with prognosis selection. Thirteen genes were selected for qPCR validation using those initial fifteen samples plus additional thirty-six samples. RESULTS: A total of 108 genes were associated with poor prognosis, independent of tumor staging. Using systems biology, we suggest that this panel reflects the dampening of immune/inflammatory response in the tumor microenvironment level and a shift to Th2/M2 activity. A gene trio (OLR1, CXCL11 and ADAMDEC1) was identified as an independent marker of prognosis, being the last two markers validated in an independent patient cohort. CONCLUSIONS: We determined a panel of three genes with prognostic value in gastric cancer, which should be further investigated. A gene expression profile suggestive of a dysfunctional inflammatory response was associated with unfavorable prognosis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00535-013-0904-0) contains supplementary material, which is available to authorized users. Springer Japan 2013-11-12 2014 /pmc/articles/PMC4223540/ /pubmed/24217965 http://dx.doi.org/10.1007/s00535-013-0904-0 Text en © The Author(s) 2013 https://creativecommons.org/licenses/by-nc/2.5/ Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article—Alimentary Tract
Pasini, Fatima Solange
Zilberstein, Bruno
Snitcovsky, Igor
Roela, Rosimeire Aparecida
Mangone, Flavia R. Rotea
Ribeiro, Ulysses
Nonogaki, Suely
Brito, Glauber Costa
Callegari, Giovanna D.
Cecconello, Ivan
Alves, Venancio Avancini Ferreira
Eluf-Neto, José
Chammas, Roger
Federico, Miriam Hatsue Honda
A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
title A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
title_full A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
title_fullStr A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
title_full_unstemmed A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
title_short A gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
title_sort gene expression profile related to immune dampening in the tumor microenvironment is associated with poor prognosis in gastric adenocarcinoma
topic Original Article—Alimentary Tract
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4223540/
https://www.ncbi.nlm.nih.gov/pubmed/24217965
http://dx.doi.org/10.1007/s00535-013-0904-0
work_keys_str_mv AT pasinifatimasolange ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT zilbersteinbruno ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT snitcovskyigor ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT roelarosimeireaparecida ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT mangoneflaviarrotea ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT ribeiroulysses ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT nonogakisuely ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT britoglaubercosta ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT callegarigiovannad ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT cecconelloivan ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT alvesvenancioavanciniferreira ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT elufnetojose ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT chammasroger ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT federicomiriamhatsuehonda ageneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT pasinifatimasolange geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT zilbersteinbruno geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT snitcovskyigor geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT roelarosimeireaparecida geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT mangoneflaviarrotea geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT ribeiroulysses geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT nonogakisuely geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT britoglaubercosta geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT callegarigiovannad geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT cecconelloivan geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT alvesvenancioavanciniferreira geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT elufnetojose geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT chammasroger geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma
AT federicomiriamhatsuehonda geneexpressionprofilerelatedtoimmunedampeninginthetumormicroenvironmentisassociatedwithpoorprognosisingastricadenocarcinoma