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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.

作者信息

Lu Keqiang, Yuan Xingxing, Zhao Lingling, Wang Bingyu, Zhang Yali

机构信息

Department of Gastroenterology, Heilongjiang Academy of Traditional Chinese Medicine, Harbin, China.

出版信息

Front Genet. 2023 Jan 4;13:996180. doi: 10.3389/fgene.2022.996180. eCollection 2022.


DOI:10.3389/fgene.2022.996180
PMID:36685952
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9845395/
Abstract

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. 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. 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. 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.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/4c250c79cb56/fgene-13-996180-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/f018e9805d4c/fgene-13-996180-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/62bc8698e894/fgene-13-996180-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/886c2714856b/fgene-13-996180-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/152f47faf419/fgene-13-996180-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/50a92167c204/fgene-13-996180-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/42930289d74f/fgene-13-996180-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/01f07b825a9d/fgene-13-996180-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/4c250c79cb56/fgene-13-996180-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/f018e9805d4c/fgene-13-996180-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/62bc8698e894/fgene-13-996180-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/886c2714856b/fgene-13-996180-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/152f47faf419/fgene-13-996180-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/50a92167c204/fgene-13-996180-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/42930289d74f/fgene-13-996180-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/01f07b825a9d/fgene-13-996180-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/4c250c79cb56/fgene-13-996180-g008.jpg

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引用本文的文献

[1]
Role of non-coding RNA-regulated ferroptosis in colorectal cancer.

Cell Death Discov. 2025-7-8

[2]
Identification and validation of susceptibility modules and hub genes of adrenocortical carcinoma through WGCNA and machine learning.

Discov Oncol. 2025-5-3

[3]
Post-transcriptional control drives Aurora kinase A expression in human cancers.

PLoS One. 2024

[4]
Identification of key genes and pathways in adrenocortical carcinoma: evidence from bioinformatic analysis.

Front Endocrinol (Lausanne). 2023

本文引用的文献

[1]
Identification of an integrated kinase-related prognostic gene signature associated with tumor immune microenvironment in human uterine corpus endometrial carcinoma.

Front Oncol. 2022-9-7

[2]
Fisher discriminant model based on LASSO logistic regression for computed tomography imaging diagnosis of pelvic rhabdomyosarcoma in children.

Sci Rep. 2022-9-17

[3]
Disorders of the adrenal cortex: Genetic and molecular aspects.

Front Endocrinol (Lausanne). 2022

[4]
Immune Checkpoint Inhibitors Do Not Increase Short-Term Risk of Hypertension in Cancer Patients: a Systematic Literature Review and Meta-Analysis.

Hypertension. 2022-11

[5]
The molecular mechanisms of ferroptosis and its role in glioma progression and treatment.

Front Oncol. 2022-8-16

[6]
Safety and efficacy of retreatment with immune checkpoint inhibitors in non-small cell lung cancer: a systematic review and meta-analysis.

Transl Lung Cancer Res. 2022-8

[7]
Combination of AURKA inhibitor and HSP90 inhibitor to treat breast cancer with AURKA overexpression and TP53 mutations.

Med Oncol. 2022-9-7

[8]
Polymorphisms in ERCC4 and ERCC5 and risk of cancers: Systematic research synopsis, meta-analysis, and epidemiological evidence.

Front Oncol. 2022-8-11

[9]
AURKA is a prognostic potential therapeutic target in skin cutaneous melanoma modulating the tumor microenvironment, apoptosis, and hypoxia.

J Cancer Res Clin Oncol. 2023-7

[10]
New endpoints in adrenocortical carcinoma studies: a mini review.

Endocrine. 2022-9

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