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通过综合生物信息学分析鉴定与乳腺癌相关的枢纽基因和小分子治疗药物。

Identification of hub genes and small molecule therapeutic drugs related to breast cancer with comprehensive bioinformatics analysis.

作者信息

Hao Mingqian, Liu Wencong, Ding Chuanbo, Peng Xiaojuan, Zhang Yue, Chen Huiying, Dong Ling, Liu Xinglong, Zhao Yingchun, Chen Xueyan, Khatoon Sadia, Zheng Yinan

机构信息

School of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, Jilin, China.

出版信息

PeerJ. 2020 Sep 29;8:e9946. doi: 10.7717/peerj.9946. eCollection 2020.

Abstract

Breast cancer is one of the most common malignant tumors among women worldwide and has a high morbidity and mortality. This research aimed to identify hub genes and small molecule drugs for breast cancer by integrated bioinformatics analysis. After downloading multiple gene expression datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, 283 overlapping differentially expressed genes (DEGs) significantly enriched in different cancer-related functions and pathways were obtained using LIMMA, VennDiagram and ClusterProfiler packages of R. We then analyzed the topology of protein-protein interaction (PPI) network with overlapping DEGs and further obtained six hub genes (RRM2, CDC20, CCNB2, BUB1B, CDK1, and CCNA2) from the network via STRING and Cytoscape. Subsequently, we conducted genes expression verification, genetic alterations evaluation, immune infiltration prediction, clinicopathological parameters analysis, identification of transcriptional and post-transcriptional regulatory molecules, and survival analysis for these hub genes. Meanwhile, 29 possible drug candidates (e.g., Cladribine, Gallium nitrate, Alvocidib, 1β-hydroxyalantolactone, Berberine hydrochloride, Nitidine chloride) were identified from the DGIdb database and the GSE85871 dataset. In addition, some transcription factors and miRNAs (e.g., E2F1, PTTG1, TP53, ZBTB16, hsa-miR-130a-3p, hsa-miR-204-5p) targeting hub genes were identified as key regulators in the progression of breast cancer. In conclusion, our study identified six hub genes and 29 potential drug candidates for breast cancer. These findings may advance understanding regarding the diagnosis, prognosis and treatment of breast cancer.

摘要

乳腺癌是全球女性中最常见的恶性肿瘤之一,发病率和死亡率都很高。本研究旨在通过综合生物信息学分析确定乳腺癌的关键基因和小分子药物。从癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)下载多个基因表达数据集后,使用R语言的LIMMA、VennDiagram和ClusterProfiler软件包获得了283个重叠差异表达基因(DEG),这些基因在不同的癌症相关功能和通路中显著富集。然后,我们用重叠的DEG分析了蛋白质-蛋白质相互作用(PPI)网络的拓扑结构,并通过STRING和Cytoscape软件从该网络中进一步获得了六个关键基因(RRM2、CDC20、CCNB2、BUB1B、CDK1和CCNA2)。随后,我们对这些关键基因进行了基因表达验证、基因改变评估、免疫浸润预测、临床病理参数分析、转录和转录后调控分子鉴定以及生存分析。同时,从DGIdb数据库和GSE85871数据集中鉴定出29种可能的候选药物(如克拉屈滨、硝酸镓、阿沃西地、1β-羟基土木香内酯、盐酸小檗碱、氯化两面针碱)。此外,一些靶向关键基因的转录因子和微小RNA(如E2F1、PTTG1、TP53、ZBTB16、hsa-miR-130a-3p、hsa-miR-204-5p)被确定为乳腺癌进展中的关键调节因子。总之,我们的研究确定了六个乳腺癌关键基因和29种潜在候选药物。这些发现可能会促进对乳腺癌诊断、预后和治疗的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b095/7556247/ef6b153c0a47/peerj-08-9946-g001.jpg

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