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基于生物信息学分析的2型神经纤维瘤病相关前庭神经鞘瘤的基因表达、网络分析及药物发现

Gene Expression, Network Analysis, and Drug Discovery of Neurofibromatosis Type 2-Associated Vestibular Schwannomas Based on Bioinformatics Analysis.

作者信息

Huang Qiao, Zhai Si-Jia, Liao Xing-Wei, Liu Yu-Chao, Yin Shi-Hua

机构信息

Department of Otolaryngology & Head and Neck Surgery, The Second Affiliated Hospital of Guangxi Medical University, Nanning 530007, China.

出版信息

J Oncol. 2020 Jul 15;2020:5976465. doi: 10.1155/2020/5976465. eCollection 2020.

DOI:10.1155/2020/5976465
PMID:32733557
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7378604/
Abstract

Neurofibromatosis Type 2- (NF2-) associated vestibular schwannomas (VSs) are histologically benign tumors. This study aimed to determine disease-related genes, pathways, and potential therapeutic drugs associated with NF2-VSs using the bioinformatics method. Microarray data of GSE108524 were downloaded from the Gene Expression Omnibus (GEO) database, and differentially expressed genes (DEGs) were screened using GEO2R. The functional enrichment and pathway enrichment of DEGs were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes Genomes (KEGG). Furthermore, the STRING and Cytoscape were used to analyze the protein-protein interaction (PPI) network of all differentially expressed genes and identify hub genes. Finally, the enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in NF2-associated VSs. A total of 542 DEGs were identified, including 13 upregulated and 329 downregulated genes, which were mainly enriched in terms of focal adhesion, PI3K-Akt signaling pathway, ECM-receptor interaction, Toll-like receptor signaling pathway, Rap1 signaling pathway, and regulation of actin cytoskeleton. 28 hub genes were identified based on the subset of PPI network, and 31 drugs were selected based on the Drug-Gene Interaction database. Drug discovery using bioinformatics methods facilitates the identification of existing or potential therapeutic drugs to improve NF2 treatment.

摘要

2型神经纤维瘤病(NF2)相关的前庭神经鞘瘤(VSs)是组织学上的良性肿瘤。本研究旨在使用生物信息学方法确定与NF2-VSs相关的疾病相关基因、信号通路和潜在治疗药物。从基因表达综合数据库(GEO)下载GSE108524的微阵列数据,并使用GEO2R筛选差异表达基因(DEGs)。使用基因本体论(GO)和京都基因与基因组百科全书(KEGG)对DEGs进行功能富集和通路富集分析。此外,利用STRING和Cytoscape分析所有差异表达基因的蛋白质-蛋白质相互作用(PPI)网络并鉴定枢纽基因。最后,针对药物-基因相互作用数据库查询属于已鉴定通路的富集基因集,以寻找可用于NF2相关VSs局部治疗的候选药物。共鉴定出542个DEGs,包括13个上调基因和329个下调基因,这些基因主要富集于粘着斑、PI3K-Akt信号通路、细胞外基质-受体相互作用、Toll样受体信号通路、Rap1信号通路以及肌动蛋白细胞骨架调节。基于PPI网络子集鉴定出28个枢纽基因,并根据药物-基因相互作用数据库选择了31种药物。利用生物信息学方法进行药物发现有助于识别现有或潜在的治疗药物,以改善NF2的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/b3d5d008fb95/JO2020-5976465.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/5a0cf777aa37/JO2020-5976465.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/e17d9bf7e4ed/JO2020-5976465.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/9d2b2a0915bb/JO2020-5976465.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/b3d5d008fb95/JO2020-5976465.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/5a0cf777aa37/JO2020-5976465.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/e17d9bf7e4ed/JO2020-5976465.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/9d2b2a0915bb/JO2020-5976465.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4cf/7378604/b3d5d008fb95/JO2020-5976465.004.jpg

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