通过生物信息学工具筛选与乳腺癌相关的潜在中心基因和关键途径。
Screening of potential hub genes and key pathways associated with breast cancer by bioinformatics tools.
发表日期:2023 Mar 17
作者:
Abdelkader Oumeddour
来源:
Cellular & Molecular Immunology
摘要:
乳腺癌(BC)仍然是全球女性死于癌症相关的主要原因。开发新的靶向治疗方法以提高患者的生存率仍是一个不断发展的领域。本研究旨在确定参与BC进展的新的生物标志物,以作为潜在的靶向治疗方法。利用GEO2R工具和Venn图软件,从GSE55715、GSE124646和GSE87049三个基因表达数据集中选择差异表达基因(DEGs)。然后使用DAVID软件进行基因本体和KEGG通路分析,使用STRING构建PPI网络并使用Cytoscape软件进行可视化,使用cytoHubba插件提取关键基因。使用Kaplan-Meier PLOTTER对存活分析,使用GEPIA2工具验证BC中关键基因的表达,使用NetworkAnalyst数据库确定关键基因的转录因子。最后,使用TIMER工具探索与相关基因的肿瘤免疫细胞浸润水平。在三个数据集中共鉴定出146个DEGs,其中60个上调基因富集于细胞周期,86个下调基因主要富集于TNF信号通路和癌症通路。鉴定出10个基因:BUB1、CDK1、HMMR、MAD2L1、CEP55、AURKA、CCNB2、TPX2、MELK和KIF20A。除CDK1之外,如果核心基因的高表达与BC的不良生存相关,并由涉及DNA结合活性和转录调节的多个转录因子调节。免疫细胞的浸润水平与核心基因呈正相关,尤其是巨噬细胞和CD4 + T细胞。该研究确定了新的可靠分子生物标志物,可作为BC治疗的潜在治疗靶点。Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
Breast cancer (BC) remains the leading cause of cancer-related death in women worldwide. The development of new targeted therapies that may improve patient survival remains an area of growing interest. This study aimed to identify new biomarkers involved in BC progression that could be used as potential targeted therapies. DEGs were selected from three gene expression profiles, GSE55715, GSE124646, and GSE87049, using the GEO2R tool and Venn diagram software. Gene Ontology and KEGG pathways were then performed using DAVID software. Next, the PPI network was constructed using STRING and visualized using Cytoscape software, and hub genes were extracted using the cytoHubba plug-in. Survival analysis was performed using the Kaplan-Meier Plotter, while the expression of hub genes in BC was verified using the GEPIA2 tool. Finally, transcription the factors of hub genes were determined using the NetworkAnalyst database, and the TIMER tool was employed to explore the infiltration levels of tumor immune cells with related genes. A total of 146 DEGs were identified in the three datasets, including 60 upregulated genes that were enriched in the cell cycle, and 86 downregulated genes that were mainly enriched in the TNF signaling pathway and pathways in cancer. Ten genes were identified: BUB1, CDK1, HMMR, MAD2L1, CEP55, AURKA, CCNB2, TPX2, MELK, and KIF20A. The overexpression of hub genes, except CDK1, was associated with poor survival in BC and was regulated by several transcription factors involved in DNA binding activity and transcription regulation. The infiltration levels of immune cells were positively correlated with hub genes, particularly macrophages and CD4+ T cells. This study identified new reliable molecular biomarkers that can serve as potential therapeutic targets for BC treatment.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.