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 <i>GATA4</i> 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 <i>TP53</i>...

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Main Authors: Berenika Trąbska-Kluch, Marcin Braun, Magdalena Orzechowska, Sylwia Paszek, Alina Zuchowska, Julia Sołek, Adam Kluska, Jacek Fijuth, Dorota Jesionek-Kupnicka, Izabela Zawlik
Format: Article
Language:English
Published: MDPI AG 2023-05-01
Series:Genes
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Online Access:https://www.mdpi.com/2073-4425/14/6/1146
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Summary:Background: Primary glioblastoma is characterized by an extremely poor prognosis. The promoter methylation of <i>GATA4</i> 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 <i>TP53</i> and GATA4 in normal human astrocytes. Nevertheless, the impact of <i>GATA4</i> alterations with linkage to <i>TP53</i> changes in gliomagenesis is poorly understood. This study aimed to evaluate GATA4 protein expression, <i>GATA4</i> promoter methylation, p53 expression, <i>TP53</i> 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 <i>GATA4</i> and <i>TP53</i> promoter methylations were analyzed via methylation-specific PCR. <i>TP53</i> 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 <i>TP53</i> 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. <i>GATA4</i> 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 <i>GATA4</i> promoter methylation. GATA4 alone has no influence on survival time in glioblastoma patients.
ISSN:2073-4425