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预测AURKA作为鼻咽癌的新型治疗靶点:基于生物信息学和验证的综合分析

Predicting AURKA as a novel therapeutic target for NPC: A comprehensive analysis based on bioinformatics and validation.

作者信息

Huang Chaobin, Chen Lin, Zhang Yiping, Wang Liyan, Zheng Wei, Peng Fengying, Xu Yuanji

机构信息

Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.

College of Clinical Medicine for Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian, China.

出版信息

Front Genet. 2022 Aug 22;13:926546. doi: 10.3389/fgene.2022.926546. eCollection 2022.

DOI:10.3389/fgene.2022.926546
PMID:36072667
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9441489/
Abstract

This study comprehensively explored the clinical function of Aurora kinase A () gene in nasopharyngeal carcinoma (NPC) and analyzed its potential as a therapeutic target in cancer. Data were downloaded from GEO, STRING, GTEx, and CellMiner databases, and subjected to multiple bioinformatic analyses, including differential expression analysis, WCGNA, gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), miRNA-hub gene regulatory network analysis, immune cell infiltration, and drug sensitivity analysis. In-depth analysis of gene expression in NPC and its corresponding clinicopathological features was performed to explore its potential as a therapeutic target. Moreover, gene expression in NPC was validated by qRT-PCR in 21 NPC tissues and 17 normal nasopharyngeal epithelial tissues. was highly expressed in NPC tissues. Enrichment analysis of and its co-expressed hub genes indicated their oncogenic role in NPC and their potential involvement in cancer-promoting processes through histone kinase activity and microtubule motility activity, cell cycle, and p53 signaling pathways. high expression group had greater infiltration of neutrophils, macrophages M2, and dendritic cells resting and less infiltration of T cells CD4 naïve and T cells γδ. Drug susceptibility analysis found that dacarbazine, R-306465, vorinostat, and other antitumor drugs that act on the cell cycle were closely related to . qRT-PCR verified the high expression of in NPC tissues ( < 0.05). We confirmed upregulation of in NPC tissues. Our results support an oncogenic role of in the context of NPC, and indicate its potential role as a novel therapeutic target.

摘要

本研究全面探讨了极光激酶A(Aurora kinase A,AURKA)基因在鼻咽癌(NPC)中的临床功能,并分析了其作为癌症治疗靶点的潜力。数据从GEO、STRING、GTEx和CellMiner数据库下载,并进行了多种生物信息学分析,包括差异表达分析、加权基因共表达网络分析(WCGNA)、基因本体论(GO)、京都基因与基因组百科全书(KEGG)、基因集富集分析(GSEA)、基因集变异分析(GSVA)、miRNA-枢纽基因调控网络分析、免疫细胞浸润和药物敏感性分析。对NPC中AURKA基因表达及其相应临床病理特征进行深入分析,以探索其作为治疗靶点的潜力。此外,通过qRT-PCR在21例NPC组织和17例正常鼻咽上皮组织中验证了AURKA基因在NPC中的表达。AURKA在NPC组织中高表达。对AURKA及其共表达的枢纽基因的富集分析表明,它们在NPC中具有致癌作用,并可能通过组蛋白激酶活性和微管运动活性、细胞周期和p53信号通路参与癌症促进过程。AURKA高表达组中性粒细胞、M2巨噬细胞和静息树突状细胞的浸润较多,而初始CD4 T细胞和γδ T细胞的浸润较少。药物敏感性分析发现,达卡巴嗪、R-306465、伏立诺他等作用于细胞周期的抗肿瘤药物与AURKA密切相关。qRT-PCR验证了AURKA在NPC组织中的高表达(P<0.05)。我们证实了NPC组织中AURKA的上调。我们的结果支持AURKA在NPC背景下的致癌作用,并表明其作为新型治疗靶点的潜在作用。

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ALDH1B1 predicts poor survival for locally advanced nasopharyngeal carcinoma patients.醛脱氢酶1B1(ALDH1B1)预示局部晚期鼻咽癌患者的预后不良。
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The pro-tumorigenic activity of p38γ overexpression in nasopharyngeal carcinoma.
使用血清氧化应激标志物和极光激酶A(AURKA)预测鼻咽癌的新型诊断列线图模型的开发与验证
Cancer Manag Res. 2023 Sep 27;15:1053-1062. doi: 10.2147/CMAR.S402572. eCollection 2023.
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Front Med (Lausanne). 2023 Feb 17;10:1120693. doi: 10.3389/fmed.2023.1120693. eCollection 2023.
p38γ 过表达在鼻咽癌中的促肿瘤生成活性。
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