Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer

Autores
Cerda Opazo, Paulina; Valenzuela Valderrama, Manuel; Wichmann, Ignacio; Rodríguez, Andrés; Contreras Reyes, Daniel; Fernandez, Elmer Andres; Carrasco Aviño, Gonzalo; Corvalan, Alejandro H.; Quest, Andrew F. G.
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
BACKGROUND: The objective of the study was to determine the relationship between Survivin and Reprimo transcript/protein expression levels, and gastric cancer outcome. METHODS: In silico correlations between an agnostic set of twelve p53-dependent apoptosis and cell-cycle genes were explored in the gastric adenocarcinoma TCGA database, using cBioPortal. Findings were validated by regression analysis of RNAseq data. Separate regression analyses were performed to assess the impact of p53 status on Survivin and Reprimo. Quantitative reverse-transcription PCR (RT-qPCR) and immunohistochemistry confirmed in silico findings on fresh-frozen and paraffin-embedded gastric cancer tissues, respectively. Wild-type (AGS, SNU-1) and mutated p53 (NCI-N87) cell lines transfected with pEGFP-Survivin or pCMV6-Reprimo were evaluated by RT-qPCR and Western blotting. Kaplan-Meier method and Long-Rank test were used to assess differences in patient outcome. RESULTS: cBioPortal analysis revealed an inverse correlation between Survivin and Reprimo expression (Pearson’s r= -0.3, Spearman’s ρ= -0.55). RNAseq analyses confirmed these findings (Spearman’s ρ= -0.37, p<4.2e-09) and revealed p53 dependence in linear regression models (p<0.05). mRNA and protein levels validated these observations in clinical samples (p<0.001). In vitro analysis in cell lines demonstrated that increasing Survivin reduced Reprimo, while increasing Reprimo reduced Survivin expression, but only did so in p53 wild-type gastric cells (p<0.05). Survivin-positive but Reprimo-negative patients displayed shorter overall survival rates (p=0.047, Long Rank Test) (HR=0.32; 95%IC: 0.11-0.97; p=0.044). CONCLUSIONS: TCGA RNAseq data analysis, evaluation of clinical samples and studies in cell lines identified an inverse relationship between Survivin and Reprimo. Elevated Survivin and reduced Reprimo protein expression correlated with poor patient prognosis in gastric cancer.
Fil: Cerda Opazo, Paulina. Universidad de Chile; Chile. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Valenzuela Valderrama, Manuel. Universidad de Chile; Chile. Universidad Central de Chile. Facultad de Ciencias de la Salud; Chile
Fil: Wichmann, Ignacio. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Rodríguez, Andrés. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Contreras Reyes, Daniel. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Plataforma Bioinformática Argentina; Argentina
Fil: Carrasco Aviño, Gonzalo. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile. Universidad de Chile; Chile
Fil: Corvalan, Alejandro H.. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Quest, Andrew F. G.. Universidad de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Materia
GASTRIC CANCER
REPRIMO
SURVIVIN
TCGA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/91295
Acceder
id CONICETDig_9db036fb97a0700eaee752b9c241eea9
oai_identifier_str oai:ri.conicet.gov.ar:11336/91295
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancerCerda Opazo, PaulinaValenzuela Valderrama, ManuelWichmann, IgnacioRodríguez, AndrésContreras Reyes, DanielFernandez, Elmer AndresCarrasco Aviño, GonzaloCorvalan, Alejandro H.Quest, Andrew F. G.GASTRIC CANCERREPRIMOSURVIVINTCGAhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3BACKGROUND: The objective of the study was to determine the relationship between Survivin and Reprimo transcript/protein expression levels, and gastric cancer outcome. METHODS: In silico correlations between an agnostic set of twelve p53-dependent apoptosis and cell-cycle genes were explored in the gastric adenocarcinoma TCGA database, using cBioPortal. Findings were validated by regression analysis of RNAseq data. Separate regression analyses were performed to assess the impact of p53 status on Survivin and Reprimo. Quantitative reverse-transcription PCR (RT-qPCR) and immunohistochemistry confirmed in silico findings on fresh-frozen and paraffin-embedded gastric cancer tissues, respectively. Wild-type (AGS, SNU-1) and mutated p53 (NCI-N87) cell lines transfected with pEGFP-Survivin or pCMV6-Reprimo were evaluated by RT-qPCR and Western blotting. Kaplan-Meier method and Long-Rank test were used to assess differences in patient outcome. RESULTS: cBioPortal analysis revealed an inverse correlation between Survivin and Reprimo expression (Pearson’s r= -0.3, Spearman’s ρ= -0.55). RNAseq analyses confirmed these findings (Spearman’s ρ= -0.37, p<4.2e-09) and revealed p53 dependence in linear regression models (p<0.05). mRNA and protein levels validated these observations in clinical samples (p<0.001). In vitro analysis in cell lines demonstrated that increasing Survivin reduced Reprimo, while increasing Reprimo reduced Survivin expression, but only did so in p53 wild-type gastric cells (p<0.05). Survivin-positive but Reprimo-negative patients displayed shorter overall survival rates (p=0.047, Long Rank Test) (HR=0.32; 95%IC: 0.11-0.97; p=0.044). CONCLUSIONS: TCGA RNAseq data analysis, evaluation of clinical samples and studies in cell lines identified an inverse relationship between Survivin and Reprimo. Elevated Survivin and reduced Reprimo protein expression correlated with poor patient prognosis in gastric cancer.Fil: Cerda Opazo, Paulina. Universidad de Chile; Chile. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; ChileFil: Valenzuela Valderrama, Manuel. Universidad de Chile; Chile. Universidad Central de Chile. Facultad de Ciencias de la Salud; ChileFil: Wichmann, Ignacio. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; ChileFil: Rodríguez, Andrés. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; ChileFil: Contreras Reyes, Daniel. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; ChileFil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Plataforma Bioinformática Argentina; ArgentinaFil: Carrasco Aviño, Gonzalo. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile. Universidad de Chile; ChileFil: Corvalan, Alejandro H.. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; ChileFil: Quest, Andrew F. G.. Universidad de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; ChileImpact Journals2018-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/91295Cerda Opazo, Paulina; Valenzuela Valderrama, Manuel; Wichmann, Ignacio; Rodríguez, Andrés; Contreras Reyes, Daniel; et al.; Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer; Impact Journals; Oncotarget; 9; 16; 2-2018; 12853-128671949-2553CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.24402info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=24402&path[]=76641info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:01:04Zoai:ri.conicet.gov.ar:11336/91295instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:01:04.553CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
title Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
spellingShingle Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
Cerda Opazo, Paulina
GASTRIC CANCER
REPRIMO
SURVIVIN
TCGA
title_short Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
title_full Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
title_fullStr Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
title_full_unstemmed Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
title_sort Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
dc.creator.none.fl_str_mv Cerda Opazo, Paulina
Valenzuela Valderrama, Manuel
Wichmann, Ignacio
Rodríguez, Andrés
Contreras Reyes, Daniel
Fernandez, Elmer Andres
Carrasco Aviño, Gonzalo
Corvalan, Alejandro H.
Quest, Andrew F. G.
author Cerda Opazo, Paulina
author_facet Cerda Opazo, Paulina
Valenzuela Valderrama, Manuel
Wichmann, Ignacio
Rodríguez, Andrés
Contreras Reyes, Daniel
Fernandez, Elmer Andres
Carrasco Aviño, Gonzalo
Corvalan, Alejandro H.
Quest, Andrew F. G.
author_role author
author2 Valenzuela Valderrama, Manuel
Wichmann, Ignacio
Rodríguez, Andrés
Contreras Reyes, Daniel
Fernandez, Elmer Andres
Carrasco Aviño, Gonzalo
Corvalan, Alejandro H.
Quest, Andrew F. G.
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv GASTRIC CANCER
REPRIMO
SURVIVIN
TCGA
topic GASTRIC CANCER
REPRIMO
SURVIVIN
TCGA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv BACKGROUND: The objective of the study was to determine the relationship between Survivin and Reprimo transcript/protein expression levels, and gastric cancer outcome. METHODS: In silico correlations between an agnostic set of twelve p53-dependent apoptosis and cell-cycle genes were explored in the gastric adenocarcinoma TCGA database, using cBioPortal. Findings were validated by regression analysis of RNAseq data. Separate regression analyses were performed to assess the impact of p53 status on Survivin and Reprimo. Quantitative reverse-transcription PCR (RT-qPCR) and immunohistochemistry confirmed in silico findings on fresh-frozen and paraffin-embedded gastric cancer tissues, respectively. Wild-type (AGS, SNU-1) and mutated p53 (NCI-N87) cell lines transfected with pEGFP-Survivin or pCMV6-Reprimo were evaluated by RT-qPCR and Western blotting. Kaplan-Meier method and Long-Rank test were used to assess differences in patient outcome. RESULTS: cBioPortal analysis revealed an inverse correlation between Survivin and Reprimo expression (Pearson’s r= -0.3, Spearman’s ρ= -0.55). RNAseq analyses confirmed these findings (Spearman’s ρ= -0.37, p<4.2e-09) and revealed p53 dependence in linear regression models (p<0.05). mRNA and protein levels validated these observations in clinical samples (p<0.001). In vitro analysis in cell lines demonstrated that increasing Survivin reduced Reprimo, while increasing Reprimo reduced Survivin expression, but only did so in p53 wild-type gastric cells (p<0.05). Survivin-positive but Reprimo-negative patients displayed shorter overall survival rates (p=0.047, Long Rank Test) (HR=0.32; 95%IC: 0.11-0.97; p=0.044). CONCLUSIONS: TCGA RNAseq data analysis, evaluation of clinical samples and studies in cell lines identified an inverse relationship between Survivin and Reprimo. Elevated Survivin and reduced Reprimo protein expression correlated with poor patient prognosis in gastric cancer.
Fil: Cerda Opazo, Paulina. Universidad de Chile; Chile. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Valenzuela Valderrama, Manuel. Universidad de Chile; Chile. Universidad Central de Chile. Facultad de Ciencias de la Salud; Chile
Fil: Wichmann, Ignacio. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Rodríguez, Andrés. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Contreras Reyes, Daniel. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Fernandez, Elmer Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales; Argentina. Plataforma Bioinformática Argentina; Argentina
Fil: Carrasco Aviño, Gonzalo. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile. Universidad de Chile; Chile
Fil: Corvalan, Alejandro H.. Pontificia Universidad Católica de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
Fil: Quest, Andrew F. G.. Universidad de Chile; Chile. Centro de Estudios Avanzados de Enfermedades Crónicas; Chile
description BACKGROUND: The objective of the study was to determine the relationship between Survivin and Reprimo transcript/protein expression levels, and gastric cancer outcome. METHODS: In silico correlations between an agnostic set of twelve p53-dependent apoptosis and cell-cycle genes were explored in the gastric adenocarcinoma TCGA database, using cBioPortal. Findings were validated by regression analysis of RNAseq data. Separate regression analyses were performed to assess the impact of p53 status on Survivin and Reprimo. Quantitative reverse-transcription PCR (RT-qPCR) and immunohistochemistry confirmed in silico findings on fresh-frozen and paraffin-embedded gastric cancer tissues, respectively. Wild-type (AGS, SNU-1) and mutated p53 (NCI-N87) cell lines transfected with pEGFP-Survivin or pCMV6-Reprimo were evaluated by RT-qPCR and Western blotting. Kaplan-Meier method and Long-Rank test were used to assess differences in patient outcome. RESULTS: cBioPortal analysis revealed an inverse correlation between Survivin and Reprimo expression (Pearson’s r= -0.3, Spearman’s ρ= -0.55). RNAseq analyses confirmed these findings (Spearman’s ρ= -0.37, p<4.2e-09) and revealed p53 dependence in linear regression models (p<0.05). mRNA and protein levels validated these observations in clinical samples (p<0.001). In vitro analysis in cell lines demonstrated that increasing Survivin reduced Reprimo, while increasing Reprimo reduced Survivin expression, but only did so in p53 wild-type gastric cells (p<0.05). Survivin-positive but Reprimo-negative patients displayed shorter overall survival rates (p=0.047, Long Rank Test) (HR=0.32; 95%IC: 0.11-0.97; p=0.044). CONCLUSIONS: TCGA RNAseq data analysis, evaluation of clinical samples and studies in cell lines identified an inverse relationship between Survivin and Reprimo. Elevated Survivin and reduced Reprimo protein expression correlated with poor patient prognosis in gastric cancer.
publishDate 2018
dc.date.none.fl_str_mv 2018-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/91295
Cerda Opazo, Paulina; Valenzuela Valderrama, Manuel; Wichmann, Ignacio; Rodríguez, Andrés; Contreras Reyes, Daniel; et al.; Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer; Impact Journals; Oncotarget; 9; 16; 2-2018; 12853-12867
1949-2553
CONICET Digital
CONICET
url http://hdl.handle.net/11336/91295
identifier_str_mv Cerda Opazo, Paulina; Valenzuela Valderrama, Manuel; Wichmann, Ignacio; Rodríguez, Andrés; Contreras Reyes, Daniel; et al.; Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer; Impact Journals; Oncotarget; 9; 16; 2-2018; 12853-12867
1949-2553
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.18632/oncotarget.24402
info:eu-repo/semantics/altIdentifier/url/http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=24402&path[]=76641
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Impact Journals
publisher.none.fl_str_mv Impact Journals
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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