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Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival

Cancer stem cell (CSC) based gene expression signatures are associated with prognosis in various tumour types and CSCs are suggested to be particularly drug resistant. The aim of our study was first, to determine the prognostic significance of CSC-related gene expression in residual tumour cells of...

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Autores principales: Bauer, Lukas, Langer, Rupert, Becker, Karen, Hapfelmeier, Alexander, Ott, Katja, Novotny, Alexander, Höfler, Heinz, Keller, Gisela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438181/
https://www.ncbi.nlm.nih.gov/pubmed/22970250
http://dx.doi.org/10.1371/journal.pone.0044566
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author Bauer, Lukas
Langer, Rupert
Becker, Karen
Hapfelmeier, Alexander
Ott, Katja
Novotny, Alexander
Höfler, Heinz
Keller, Gisela
author_facet Bauer, Lukas
Langer, Rupert
Becker, Karen
Hapfelmeier, Alexander
Ott, Katja
Novotny, Alexander
Höfler, Heinz
Keller, Gisela
author_sort Bauer, Lukas
collection PubMed
description Cancer stem cell (CSC) based gene expression signatures are associated with prognosis in various tumour types and CSCs are suggested to be particularly drug resistant. The aim of our study was first, to determine the prognostic significance of CSC-related gene expression in residual tumour cells of neoadjuvant-treated gastric cancer (GC) patients. Second, we wished to examine, whether expression alterations between pre- and post-therapeutic tumour samples exist, consistent with an enrichment of drug resistant tumour cells. The expression of 44 genes was analysed in 63 formalin-fixed, paraffin embedded tumour specimens with partial tumour regression (10–50% residual tumour) after neoadjuvant chemotherapy by quantitative real time PCR low-density arrays. A signature of combined GSK3B (high), β-catenin (CTNNB1) (high) and NOTCH2 (low) expression was strongly correlated with better patient survival (p<0.001). A prognostic relevance of these genes was also found analysing publically available gene expression data. The expression of 9 genes was compared between pre-therapeutic biopsies and post-therapeutic resected specimens. A significant post-therapeutic increase in NOTCH2, LGR5 and POU5F1 expression was found in tumours with different tumour regression grades. No significant alterations were observed for GSK3B and CTNNB1. Immunohistochemical analysis demonstrated a chemotherapy-associated increase in the intensity of NOTCH2 staining, but not in the percentage of NOTCH2. Taken together, the GSK3B, CTNNB1 and NOTCH2 expression signature is a novel, promising prognostic parameter for GC. The results of the differential expression analysis indicate a prominent role for NOTCH2 and chemotherapy resistance in GC, which seems to be related to an effect of the drugs on NOTCH2 expression rather than to an enrichment of NOTCH2 expressing tumour cells.
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spelling pubmed-34381812012-09-11 Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival Bauer, Lukas Langer, Rupert Becker, Karen Hapfelmeier, Alexander Ott, Katja Novotny, Alexander Höfler, Heinz Keller, Gisela PLoS One Research Article Cancer stem cell (CSC) based gene expression signatures are associated with prognosis in various tumour types and CSCs are suggested to be particularly drug resistant. The aim of our study was first, to determine the prognostic significance of CSC-related gene expression in residual tumour cells of neoadjuvant-treated gastric cancer (GC) patients. Second, we wished to examine, whether expression alterations between pre- and post-therapeutic tumour samples exist, consistent with an enrichment of drug resistant tumour cells. The expression of 44 genes was analysed in 63 formalin-fixed, paraffin embedded tumour specimens with partial tumour regression (10–50% residual tumour) after neoadjuvant chemotherapy by quantitative real time PCR low-density arrays. A signature of combined GSK3B (high), β-catenin (CTNNB1) (high) and NOTCH2 (low) expression was strongly correlated with better patient survival (p<0.001). A prognostic relevance of these genes was also found analysing publically available gene expression data. The expression of 9 genes was compared between pre-therapeutic biopsies and post-therapeutic resected specimens. A significant post-therapeutic increase in NOTCH2, LGR5 and POU5F1 expression was found in tumours with different tumour regression grades. No significant alterations were observed for GSK3B and CTNNB1. Immunohistochemical analysis demonstrated a chemotherapy-associated increase in the intensity of NOTCH2 staining, but not in the percentage of NOTCH2. Taken together, the GSK3B, CTNNB1 and NOTCH2 expression signature is a novel, promising prognostic parameter for GC. The results of the differential expression analysis indicate a prominent role for NOTCH2 and chemotherapy resistance in GC, which seems to be related to an effect of the drugs on NOTCH2 expression rather than to an enrichment of NOTCH2 expressing tumour cells. Public Library of Science 2012-09-10 /pmc/articles/PMC3438181/ /pubmed/22970250 http://dx.doi.org/10.1371/journal.pone.0044566 Text en © 2012 Bauer et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Bauer, Lukas
Langer, Rupert
Becker, Karen
Hapfelmeier, Alexander
Ott, Katja
Novotny, Alexander
Höfler, Heinz
Keller, Gisela
Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival
title Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival
title_full Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival
title_fullStr Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival
title_full_unstemmed Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival
title_short Expression Profiling of Stem Cell-Related Genes in Neoadjuvant-Treated Gastric Cancer: A NOTCH2, GSK3B and β-catenin Gene Signature Predicts Survival
title_sort expression profiling of stem cell-related genes in neoadjuvant-treated gastric cancer: a notch2, gsk3b and β-catenin gene signature predicts survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3438181/
https://www.ncbi.nlm.nih.gov/pubmed/22970250
http://dx.doi.org/10.1371/journal.pone.0044566
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