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

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...

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Autores principales: Cerda-Opazo, P., Valenzuela-Valderrama, M., Wichmann, I., Rodríguez, A., Contreras-Reyes, D., Fernández, E.A., Carrasco-Aviño, G., Corvalán, A.H., Quest, A.F.G.
Formato: JOUR
Materias:
Gastric cancer
Reprimo
Survivin
TCGA
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_19492553_v9_n16_p12853_CerdaOpazo
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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spelling todo:paper_19492553_v9_n16_p12853_CerdaOpazo2023-10-03T16:37:20Z Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer Cerda-Opazo, P. Valenzuela-Valderrama, M. Wichmann, I. Rodríguez, A. Contreras-Reyes, D. Fernández, E.A. Carrasco-Aviño, G. Corvalán, A.H. Quest, A.F.G. Gastric cancer Reprimo Survivin TCGA 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 paraffinembedded 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. © Cerda-Opazo et al. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_19492553_v9_n16_p12853_CerdaOpazo
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Gastric cancer
Reprimo
Survivin
TCGA
spellingShingle Gastric cancer
Reprimo
Survivin
TCGA
Cerda-Opazo, P.
Valenzuela-Valderrama, M.
Wichmann, I.
Rodríguez, A.
Contreras-Reyes, D.
Fernández, E.A.
Carrasco-Aviño, G.
Corvalán, A.H.
Quest, A.F.G.
Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
topic_facet Gastric cancer
Reprimo
Survivin
TCGA
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 paraffinembedded 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. © Cerda-Opazo et al.
format JOUR
author Cerda-Opazo, P.
Valenzuela-Valderrama, M.
Wichmann, I.
Rodríguez, A.
Contreras-Reyes, D.
Fernández, E.A.
Carrasco-Aviño, G.
Corvalán, A.H.
Quest, A.F.G.
author_facet Cerda-Opazo, P.
Valenzuela-Valderrama, M.
Wichmann, I.
Rodríguez, A.
Contreras-Reyes, D.
Fernández, E.A.
Carrasco-Aviño, G.
Corvalán, A.H.
Quest, A.F.G.
author_sort Cerda-Opazo, P.
title Inverse expression of survivin and reprimo correlates with poor patient prognosis in gastric cancer
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
url http://hdl.handle.net/20.500.12110/paper_19492553_v9_n16_p12853_CerdaOpazo
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