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Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment

Background: The only curative option for patients with locally or locally advanced adrenocortical carcinoma is primary tumor curative sexual resection (ACC). However, overall survival remains low, with most deaths occurring within the first 2 years following surgery. The 5-year survival rate after s...

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Autores principales: Lu, Keqiang, Yuan, Xingxing, Zhao, Lingling, Wang, Bingyu, Zhang, Yali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845395/
https://www.ncbi.nlm.nih.gov/pubmed/36685952
http://dx.doi.org/10.3389/fgene.2022.996180
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author Lu, Keqiang
Yuan, Xingxing
Zhao, Lingling
Wang, Bingyu
Zhang, Yali
author_facet Lu, Keqiang
Yuan, Xingxing
Zhao, Lingling
Wang, Bingyu
Zhang, Yali
author_sort Lu, Keqiang
collection PubMed
description Background: The only curative option for patients with locally or locally advanced adrenocortical carcinoma is primary tumor curative sexual resection (ACC). However, overall survival remains low, with most deaths occurring within the first 2 years following surgery. The 5-year survival rate after surgery is less than 30%. As a result, more accurate prognosis-related predictive biomarkers must be investigated urgently to detect patients’ disease status after surgery. Methods: Data from FerrDb were obtained to identify ferroptosis-related genes, and ACC gene expression profiles were collected from the GEO database to find differentially expressed ACC ferroptosis-related genes using differential expression analysis. The DEFGs were subjected to Gene Ontology gene enrichment analysis and KEGG signaling pathway enrichment analysis. PPI network building and predictive analysis were used to filter core genes. The expression of critical genes in ACC pathological stage and pan-cancer was then investigated. In recent years, immune-related factors, DNA repair genes, and methyltransferase genes have been employed in diagnosing and prognosis of different malignancies. Cancer cells are mutated due to DNA repair genes, and highly expressed DNA repair genes promote cancer. Dysregulation of methyltransferase genes and Immune-related factors, which are shown to be significantly expressed in numerous malignancies, also plays a crucial role in cancer. As a result, we investigated the relationship of AURKA with immunological checkpoints, DNA repair genes, and methyltransferases in pan-cancer. Result: The DEGs found in the GEO database were crossed with ferroptosis-related genes, yielding 42 differentially expressed ferroptosis-related genes. Six of these 42 genes, particularly AURKA, are linked to the prognosis of ACC. AURKA expression was significantly correlated with poor prognosis in patients with multiple cancers, and there was a significant positive correlation with Th2 cells. Furthermore, AURKA expression was positively associated with tumor immune infiltration in Lung adenocarcinoma (LUAD), Liver hepatocellular carcinoma (LIHC), Sarcoma (SARC), Esophageal carcinoma (ESCA), and Stomach adenocarcinoma (STAD), but negatively correlated with the immune score, matrix score, and calculated score in these tumors. Further investigation into the relationship between AURKA expression and immune examination gene expression revealed that AURKA could control the tumor-resistant pattern in most tumors by regulating the expression level of specific immune examination genes. Conclusion: AURKA may be an independent prognostic marker for predicting ACC patient prognosis. AURKA may play an essential role in the tumor microenvironment and tumor immunity, according to a pan-cancer analysis, and it has the potential to be a predictive biomarker for multiple cancers.
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spelling pubmed-98453952023-01-19 Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment Lu, Keqiang Yuan, Xingxing Zhao, Lingling Wang, Bingyu Zhang, Yali Front Genet Genetics Background: The only curative option for patients with locally or locally advanced adrenocortical carcinoma is primary tumor curative sexual resection (ACC). However, overall survival remains low, with most deaths occurring within the first 2 years following surgery. The 5-year survival rate after surgery is less than 30%. As a result, more accurate prognosis-related predictive biomarkers must be investigated urgently to detect patients’ disease status after surgery. Methods: Data from FerrDb were obtained to identify ferroptosis-related genes, and ACC gene expression profiles were collected from the GEO database to find differentially expressed ACC ferroptosis-related genes using differential expression analysis. The DEFGs were subjected to Gene Ontology gene enrichment analysis and KEGG signaling pathway enrichment analysis. PPI network building and predictive analysis were used to filter core genes. The expression of critical genes in ACC pathological stage and pan-cancer was then investigated. In recent years, immune-related factors, DNA repair genes, and methyltransferase genes have been employed in diagnosing and prognosis of different malignancies. Cancer cells are mutated due to DNA repair genes, and highly expressed DNA repair genes promote cancer. Dysregulation of methyltransferase genes and Immune-related factors, which are shown to be significantly expressed in numerous malignancies, also plays a crucial role in cancer. As a result, we investigated the relationship of AURKA with immunological checkpoints, DNA repair genes, and methyltransferases in pan-cancer. Result: The DEGs found in the GEO database were crossed with ferroptosis-related genes, yielding 42 differentially expressed ferroptosis-related genes. Six of these 42 genes, particularly AURKA, are linked to the prognosis of ACC. AURKA expression was significantly correlated with poor prognosis in patients with multiple cancers, and there was a significant positive correlation with Th2 cells. Furthermore, AURKA expression was positively associated with tumor immune infiltration in Lung adenocarcinoma (LUAD), Liver hepatocellular carcinoma (LIHC), Sarcoma (SARC), Esophageal carcinoma (ESCA), and Stomach adenocarcinoma (STAD), but negatively correlated with the immune score, matrix score, and calculated score in these tumors. Further investigation into the relationship between AURKA expression and immune examination gene expression revealed that AURKA could control the tumor-resistant pattern in most tumors by regulating the expression level of specific immune examination genes. Conclusion: AURKA may be an independent prognostic marker for predicting ACC patient prognosis. AURKA may play an essential role in the tumor microenvironment and tumor immunity, according to a pan-cancer analysis, and it has the potential to be a predictive biomarker for multiple cancers. Frontiers Media S.A. 2023-01-04 /pmc/articles/PMC9845395/ /pubmed/36685952 http://dx.doi.org/10.3389/fgene.2022.996180 Text en Copyright © 2023 Lu, Yuan, Zhao, Wang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Lu, Keqiang
Yuan, Xingxing
Zhao, Lingling
Wang, Bingyu
Zhang, Yali
Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
title Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
title_full Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
title_fullStr Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
title_full_unstemmed Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
title_short Comprehensive pan-cancer analysis and the regulatory mechanism of AURKA, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
title_sort comprehensive pan-cancer analysis and the regulatory mechanism of aurka, a gene associated with prognosis of ferroptosis of adrenal cortical carcinoma in the tumor micro-environment
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845395/
https://www.ncbi.nlm.nih.gov/pubmed/36685952
http://dx.doi.org/10.3389/fgene.2022.996180
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