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肿瘤微环境中与肾上腺皮质癌铁死亡预后相关基因AURKA的综合泛癌分析及调控机制

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.

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

对于局部或局部晚期肾上腺皮质癌患者,唯一的治愈选择是原发性肿瘤根治性切除(ACC)。然而,总体生存率仍然很低,大多数死亡发生在手术后的头2年内。手术后的5年生存率不到30%。因此,必须迫切研究更准确的预后相关预测生物标志物,以检测患者术后的疾病状态。从FerrDb获取数据以识别铁死亡相关基因,并从GEO数据库收集ACC基因表达谱,使用差异表达分析来寻找差异表达的ACC铁死亡相关基因。对差异表达铁死亡相关基因(DEFGs)进行基因本体基因富集分析和KEGG信号通路富集分析。使用蛋白质-蛋白质相互作用(PPI)网络构建和预测分析来筛选核心基因。然后研究关键基因在ACC病理分期和泛癌中的表达。近年来,免疫相关因子、DNA修复基因和甲基转移酶基因已被用于不同恶性肿瘤的诊断和预后评估。癌细胞因DNA修复基因发生突变,高度表达的DNA修复基因促进癌症发展。甲基转移酶基因和免疫相关因子的失调在许多恶性肿瘤中显著表达,在癌症中也起着关键作用。因此,我们研究了泛癌中极光激酶A(AURKA)与免疫检查点、DNA修复基因和甲基转移酶的关系。在GEO数据库中发现的差异表达基因(DEGs)与铁死亡相关基因进行交叉比对,产生了42个差异表达的铁死亡相关基因。这42个基因中的6个,特别是AURKA,与ACC的预后相关。AURKA表达与多种癌症患者的不良预后显著相关,并且与Th2细胞存在显著正相关。此外,AURKA表达在肺腺癌(LUAD)、肝细胞癌(LIHC)、肉瘤(SARC)、食管癌(ESCA)和胃腺癌(STAD)中与肿瘤免疫浸润呈正相关,但与这些肿瘤中的免疫评分、基质评分和计算评分呈负相关。进一步研究AURKA表达与免疫检查基因表达之间的关系发现,AURKA可以通过调节特定免疫检查基因的表达水平来控制大多数肿瘤的抗瘤模式。AURKA可能是预测ACC患者预后的独立预后标志物。泛癌分析表明,AURKA可能在肿瘤微环境和肿瘤免疫中起重要作用,并且有可能成为多种癌症的预测生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03f6/9845395/f018e9805d4c/fgene-13-996180-g001.jpg

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