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通过综合生物信息学分析鉴定髓母细胞瘤中的枢纽基因和小分子化合物

Identification of hub genes and small-molecule compounds in medulloblastoma by integrated bioinformatic analyses.

作者信息

Liu Zhendong, Zhang Ruotian, Sun Zhenying, Yao Jiawei, Yao Penglei, Chen Xin, Wang Xinzhuang, Gao Ming, Wan Jinzhao, Du Yiming, Zhao Shiguang

机构信息

Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.

Institute of Brain Science, Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.

出版信息

PeerJ. 2020 Apr 14;8:e8670. doi: 10.7717/peerj.8670. eCollection 2020.

Abstract

BACKGROUND

Medulloblastoma (MB) is the most common intracranial malignant tumor in children. The genes and pathways involved in the pathogenesis of MB are relatively unknown. We aimed to identify potential biomarkers and small-molecule drugs for MB.

METHODS

Gene expression profile data sets were obtained from the Gene Expression Omnibus (GEO) database and the differentially expressed genes (DEGs) were identified using the Limma package in R. Functional annotation, and cell signaling pathway analysis of DEGs was carried out using DAVID and Kobas. A protein-protein interaction network was generated using STRING. Potential small-molecule drugs were identified using CMap.

RESULT

We identified 104 DEGs (29 upregulated; 75 downregulated). Gene ontology analysis showed enrichment in the mitotic cell cycle, cell cycle, spindle, and DNA binding. Cell signaling pathway analysis identified cell cycle, HIF-1 signaling pathway, and phospholipase D signaling pathway as key pathways. SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were the prominent hub genes and their expression level were verified by RT-qPCR. Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB. The five hub genes may be targets for diagnosis and treatment of MB, and the small-molecule compounds are promising drugs for effective treatment of MB.

CONCLUSION

In this study we obtained five hub genes of MB, SYN1, CNTN2, FAIM2, MT3, and SH3GL2 were confirmed as hub genes. Meanwhile, Vorinostat, resveratrol, trichostatin A, pyrvinium, and prochlorperazine were identified as potential drugs for MB.

摘要

背景

髓母细胞瘤(MB)是儿童最常见的颅内恶性肿瘤。MB发病机制中涉及的基因和信号通路相对尚不明确。我们旨在鉴定MB的潜在生物标志物和小分子药物。

方法

从基因表达综合数据库(GEO)获取基因表达谱数据集,并使用R语言中的Limma软件包鉴定差异表达基因(DEG)。使用DAVID和Kobas对DEG进行功能注释和细胞信号通路分析。使用STRING生成蛋白质-蛋白质相互作用网络。使用CMap鉴定潜在的小分子药物。

结果

我们鉴定出104个DEG(29个上调;75个下调)。基因本体分析显示在有丝分裂细胞周期、细胞周期、纺锤体和DNA结合方面富集。细胞信号通路分析确定细胞周期、缺氧诱导因子-1信号通路和磷脂酶D信号通路为关键通路。SYN1、CNTN2(接触蛋白2)、FAIM2(Fas凋亡抑制分子2)、MT3(金属硫蛋白3)和SH3GL2(含SH3结构域的网格蛋白轻链衔接蛋白2)是突出的枢纽基因,其表达水平通过逆转录定量聚合酶链反应(RT-qPCR)得到验证。伏立诺他、白藜芦醇、曲古抑菌素A、吡维铵和丙氯拉嗪被鉴定为MB的潜在药物。这五个枢纽基因可能是MB诊断和治疗的靶点,而这些小分子化合物是有效治疗MB的有前景的药物。

结论

在本研究中,我们获得了MB的五个枢纽基因,SYN1、CNTN2(接触蛋白2)、FAIM2(Fas凋亡抑制分子2)、MT3(金属硫蛋白3)和SH3GL2被确认为枢纽基因。同时,伏立诺他、白藜芦醇、曲古抑菌素A、吡维铵和丙氯拉嗪被鉴定为MB的潜在药物。

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