Department of Natural Sciences and Life, 8 May 1945 University of Guelma, Guelma, Algeria.
Medicine (Baltimore). 2023 Mar 17;102(11):e33291. doi: 10.1097/MD.0000000000033291.
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.
乳腺癌（BC）仍然是全球女性癌症相关死亡的主要原因。开发可能提高患者生存率的新靶向治疗方法仍然是一个日益关注的领域。本研究旨在鉴定新的与 BC 进展相关的生物标志物，这些标志物可作为潜在的靶向治疗靶点。使用 GEO2R 工具和 Venn 图软件从三个基因表达谱（GSE55715、GSE124646 和 GSE87049）中选择 DEGs。然后使用 DAVID 软件进行基因本体论和 KEGG 通路分析。接下来，使用 STRING 构建 PPI 网络，并使用 Cytoscape 软件可视化，使用 cytoHubba 插件提取枢纽基因。使用 Kaplan-Meier Plotter 进行生存分析，使用 GEPIA2 工具验证 BC 中枢纽基因的表达。最后，使用 NetworkAnalyst 数据库确定枢纽基因的转录因子，并使用 TIMER 工具探索与相关基因相关的肿瘤免疫细胞的浸润水平。在三个数据集中共鉴定出 146 个 DEGs，包括 60 个上调基因，其主要富集在细胞周期中，86 个下调基因主要富集在 TNF 信号通路和癌症途径中。鉴定出 10 个基因：BUB1、CDK1、HMMR、MAD2L1、CEP55、AURKA、CCNB2、TPX2、MELK 和 KIF20A。除 CDK1 外，枢纽基因的过表达与 BC 不良预后相关，受涉及 DNA 结合活性和转录调节的几个转录因子调控。免疫细胞的浸润水平与枢纽基因呈正相关，尤其是巨噬细胞和 CD4+T 细胞。本研究鉴定出了新的可靠的分子生物标志物，可作为 BC 治疗的潜在治疗靶点。
