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Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients

Background: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes....

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Autores principales: Trąbska-Kluch, Berenika, Braun, Marcin, Orzechowska, Magdalena, Paszek, Sylwia, Zuchowska, Alina, Sołek, Julia, Kluska, Adam, Fijuth, Jacek, Jesionek-Kupnicka, Dorota, Zawlik, Izabela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298403/
https://www.ncbi.nlm.nih.gov/pubmed/37372326
http://dx.doi.org/10.3390/genes14061146
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author Trąbska-Kluch, Berenika
Braun, Marcin
Orzechowska, Magdalena
Paszek, Sylwia
Zuchowska, Alina
Sołek, Julia
Kluska, Adam
Fijuth, Jacek
Jesionek-Kupnicka, Dorota
Zawlik, Izabela
author_facet Trąbska-Kluch, Berenika
Braun, Marcin
Orzechowska, Magdalena
Paszek, Sylwia
Zuchowska, Alina
Sołek, Julia
Kluska, Adam
Fijuth, Jacek
Jesionek-Kupnicka, Dorota
Zawlik, Izabela
author_sort Trąbska-Kluch, Berenika
collection PubMed
description Background: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. Materials and Methods: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. Results: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. Conclusions: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.
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spelling pubmed-102984032023-06-28 Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients Trąbska-Kluch, Berenika Braun, Marcin Orzechowska, Magdalena Paszek, Sylwia Zuchowska, Alina Sołek, Julia Kluska, Adam Fijuth, Jacek Jesionek-Kupnicka, Dorota Zawlik, Izabela Genes (Basel) Article Background: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of GATA4 leads to the loss of its expression in many cancer types. The formation of high-grade astrocytomas can be promoted by the concurrent loss of TP53 and GATA4 in normal human astrocytes. Nevertheless, the impact of GATA4 alterations with linkage to TP53 changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, GATA4 promoter methylation, p53 expression, TP53 promoter methylation, and mutation status in patients with primary glioblastoma and to assess the possible prognostic impact of these alterations on overall survival. Materials and Methods: Thirty-one patients with primary glioblastoma were included. GATA4 and p53 expressions were determined immunohistochemically, and GATA4 and TP53 promoter methylations were analyzed via methylation-specific PCR. TP53 mutations were investigated via Sanger sequencing. Results: The prognostic value of GATA4 depends on p53 expression. Patients without GATA4 protein expression were more frequently negative for TP53 mutations and had better prognoses than the GATA4 positive patients. In patients positive for GATA4 protein expression, p53 expression was associated with the worst outcome. However, in patients positive for p53 expression, the loss of GATA4 protein expression seemed to be associated with improved prognosis. GATA4 promoter methylation was not associated with a lack of GATA4 protein expression. Conclusions: Our data indicate that there is a possibility that GATA4 could function as a prognostic factor in glioblastoma patients, but in connection with p53 expression. A lack of GATA4 expression is not dependent on GATA4 promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients. MDPI 2023-05-25 /pmc/articles/PMC10298403/ /pubmed/37372326 http://dx.doi.org/10.3390/genes14061146 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Trąbska-Kluch, Berenika
Braun, Marcin
Orzechowska, Magdalena
Paszek, Sylwia
Zuchowska, Alina
Sołek, Julia
Kluska, Adam
Fijuth, Jacek
Jesionek-Kupnicka, Dorota
Zawlik, Izabela
Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients
title Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients
title_full Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients
title_fullStr Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients
title_full_unstemmed Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients
title_short Potential Prognostic Value of GATA4 Depends on the p53 Expression in Primary Glioblastoma Patients
title_sort potential prognostic value of gata4 depends on the p53 expression in primary glioblastoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10298403/
https://www.ncbi.nlm.nih.gov/pubmed/37372326
http://dx.doi.org/10.3390/genes14061146
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