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通过生物信息学分析鉴定乳腺癌的早期诊断生物标志物。

Identification of early diagnostic biomarkers for breast cancer through bioinformatics analysis.

机构信息

Breast Department, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, Shanxi, China.

Department of Traditional Chinese Medicine, Shanxi Institute of Traditional Chinese Medicine, Taiyuan, Shanxi, China.

出版信息

Medicine (Baltimore). 2023 Sep 15;102(37):e35273. doi: 10.1097/MD.0000000000035273.

DOI:10.1097/MD.0000000000035273
PMID:37713876
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10508380/
Abstract

In the realm of clinical practice, there is currently an insufficiency of distinct biomarkers available for the detection of breast cancer. It is of utmost importance to promptly employ bioinformatics methodologies to investigate prospective biomarkers for breast cancer, with the ultimate goal of achieving early diagnosis of the disease. The initial phase of this investigation involved the identification of 2 breast cancer gene chips meeting the specified criteria within the gene expression omnibus database. Subsequently, paired data analysis was conducted on these datasets, leading to the identification of differentially expressed genes (DEGs). In addition, this study executed Gene Ontology enrichment analysis and Kyoto encyclopedia of genes and genomes pathway enrichment analysis. The subsequent stage involved the construction of a protein-protein interaction network graph using the STRING website and Cytoscape software, facilitating the calculation of Hub genes. Lastly, the UALCAN database and Kaplan-Meier survival plots were utilized to perform differential expression and survival analysis on the selected Hub genes. A total of 733 DEGs were identified from the combined analysis of 2 datasets. Among these DEGs, 441 genes were found to be downregulated, while 292 genes were upregulated. The selected DEGs underwent comprehensive analysis, including gene ontology enrichment analysis, Kyoto encyclopedia of genes and genomes pathway enrichment analysis, and establishing a protein-protein interaction network. As a result, 10 Hub genes closely associated with early diagnosis of breast cancer were identified: PDZ-binding kinase, cell cycle protein A2, cell division cycle-associated protein 8, maternal embryonic leucine zipper kinase, nucleolar and spindle-associated protein 1, BIRC5, cell cycle protein B2, hyaluronan-mediated motility receptor, mitotic arrest deficient 2-like 1, and protein regulator of cytokinesis 1. The findings of this study unveiled the significant involvement of the identified 10 Hub genes in facilitating the growth and proliferation of cancer cells, particularly cell cycle protein A2, cell division cycle-associated protein 8, maternal embryonic leucine zipper kinase, nucleolar and spindle-associated protein 1, hyaluronan-mediated motility receptor, and protein regulator of cytokinesis 1, which demonstrated a more pronounced connection with the onset and progression of breast cancer. Further analysis through differential expression and survival analysis reaffirmed their strong correlation with the incidence of breast cancer. Consequently, the investigation of these 10 pertinent Hub genes presents novel prospects for potential biomarkers and valuable insights into the early diagnosis of breast cancer.

摘要

在临床实践中,目前用于检测乳腺癌的特异性生物标志物还很缺乏。因此,急需运用生物信息学方法来寻找乳腺癌潜在的生物标志物,以期实现对该病的早期诊断。本研究首先在基因表达综合数据库中筛选出符合条件的 2 个乳腺癌基因芯片,然后对这 2 个数据集进行配对数据比较分析,找到差异表达基因(DEGs),并进行基因本体论富集分析和京都基因与基因组百科全书通路富集分析。之后借助 STRING 网站和 Cytoscape 软件构建蛋白质-蛋白质相互作用网络图,计算关键基因(Hub 基因)。最后利用 UALCAN 数据库和 Kaplan-Meier 生存曲线对筛选出的 Hub 基因进行差异表达和生存分析。通过对 2 个数据集进行联合分析,共筛选到 733 个 DEGs,其中下调基因 441 个,上调基因 292 个。对筛选出的 DEGs 进行基因本体论富集分析、京都基因与基因组百科全书通路富集分析及构建蛋白质-蛋白质相互作用网络图,找到与乳腺癌早期诊断密切相关的 10 个 Hub 基因:PDZ 结合激酶、细胞周期蛋白 A2、细胞分裂周期相关蛋白 8、母源胚胎亮氨酸拉链激酶、核仁与纺锤体相关蛋白 1、BIRC5、细胞周期蛋白 B2、透明质酸介导的运动受体、有丝分裂缺陷 2 样 1、细胞分裂调控蛋白 1。研究结果表明,这 10 个 Hub 基因在促进癌细胞生长和增殖中发挥了重要作用,尤其是细胞周期蛋白 A2、细胞分裂周期相关蛋白 8、母源胚胎亮氨酸拉链激酶、核仁与纺锤体相关蛋白 1、透明质酸介导的运动受体和细胞分裂调控蛋白 1,它们与乳腺癌的发生和发展有着更为密切的联系。通过差异表达和生存分析进一步证实了它们与乳腺癌发病率的强相关性。因此,研究这 10 个关键 Hub 基因可为乳腺癌的早期诊断提供新的潜在生物标志物和有价值的见解。

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