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Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular en...

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Autores principales: Ferreira, Wallax Augusto Silva, de Oliveira, Edivaldo Herculano Correa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222030/
https://www.ncbi.nlm.nih.gov/pubmed/35735610
http://dx.doi.org/10.3390/cimb44060169
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author Ferreira, Wallax Augusto Silva
de Oliveira, Edivaldo Herculano Correa
author_facet Ferreira, Wallax Augusto Silva
de Oliveira, Edivaldo Herculano Correa
author_sort Ferreira, Wallax Augusto Silva
collection PubMed
description Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, linking multiple pathways. Nevertheless, the expression profile and prognostic significance of GOT2 in KIRC remain unclear. This study comprehensively analyzed the transcriptional levels, epigenetic regulation, correlation with immune infiltration, and prognosis of GOT2 in KIRC using rigorous bioinformatics analysis. We discovered that the expression levels of both mRNA and protein of GOT2 were remarkably decreased in KIRC tissues in comparison with normal tissues and were also significantly related to the clinical features and prognosis of KIRC. Remarkably, low GOT2 expression was positively associated with poorer overall survival (OS) and disease-free survival (DFS). Further analysis revealed that GOT2 downregulation is driven by DNA methylation in the promoter-related CpG islands. Finally, we also shed light on the influence of GOT2 expression in immune cell infiltration, suggesting that GOT2 may be a potential prognostic marker and therapeutic target for KIRC patients.
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spelling pubmed-92220302022-06-24 Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma Ferreira, Wallax Augusto Silva de Oliveira, Edivaldo Herculano Correa Curr Issues Mol Biol Article Clear cell renal cell carcinoma (KIRC) is the most common and highly malignant pathological type of kidney cancer, characterized by a profound metabolism dysregulation. As part of aspartate biosynthesis, mitochondrial GOT2 (glutamic-oxaloacetic transaminase 2) is essential for regulating cellular energy production and biosynthesis, linking multiple pathways. Nevertheless, the expression profile and prognostic significance of GOT2 in KIRC remain unclear. This study comprehensively analyzed the transcriptional levels, epigenetic regulation, correlation with immune infiltration, and prognosis of GOT2 in KIRC using rigorous bioinformatics analysis. We discovered that the expression levels of both mRNA and protein of GOT2 were remarkably decreased in KIRC tissues in comparison with normal tissues and were also significantly related to the clinical features and prognosis of KIRC. Remarkably, low GOT2 expression was positively associated with poorer overall survival (OS) and disease-free survival (DFS). Further analysis revealed that GOT2 downregulation is driven by DNA methylation in the promoter-related CpG islands. Finally, we also shed light on the influence of GOT2 expression in immune cell infiltration, suggesting that GOT2 may be a potential prognostic marker and therapeutic target for KIRC patients. MDPI 2022-05-25 /pmc/articles/PMC9222030/ /pubmed/35735610 http://dx.doi.org/10.3390/cimb44060169 Text en © 2022 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
Ferreira, Wallax Augusto Silva
de Oliveira, Edivaldo Herculano Correa
Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma
title Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma
title_full Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma
title_fullStr Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma
title_full_unstemmed Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma
title_short Expression of GOT2 Is Epigenetically Regulated by DNA Methylation and Correlates with Immune Infiltrates in Clear-Cell Renal Cell Carcinoma
title_sort expression of got2 is epigenetically regulated by dna methylation and correlates with immune infiltrates in clear-cell renal cell carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222030/
https://www.ncbi.nlm.nih.gov/pubmed/35735610
http://dx.doi.org/10.3390/cimb44060169
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