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通过生物信息学分析鉴定胶质母细胞瘤中的关键基因和信号通路。

The identification of key genes and pathways in glioblastoma by bioinformatics analysis.

作者信息

Farsi Zahra, Allahyari Fard Najaf

机构信息

Department of Biology, Noor-Dnaesh Institute of Higher Education, Esfahan, Iran.

Department of Systems Biotechnology, National Institute of Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran.

出版信息

Mol Cell Oncol. 2023 Aug 14;10(1):2246657. doi: 10.1080/23723556.2023.2246657. eCollection 2023.

Abstract

GBM is the most common and aggressive type of brain tumor. It is classified as a grade IV tumor by the WHO, the highest grade. Prognosis is generally poor, with most patients surviving only about a year. Only 5% of patients survive longer than 5 years. Understanding the molecular mechanisms that drive GBM progression is critical for developing better diagnostic and treatment strategies. Identifying key genes involved in GBM pathogenesis is essential to fully understand the disease and develop targeted therapies. In this study two datasets, GSE108474 and GSE50161, were obtained from the Gene Expression Omnibus (GEO) to compare gene expression between GBM and normal samples. Differentially expressed genes (DEGs) were identified and analyzed. To construct a protein-protein interaction (PPI) network of the commonly up-regulated and down-regulated genes, the STRING 11.5 and Cytoscape 3.9.1 were utilized. Key genes were identified through this network analysis. The GEPIA database was used to confirm the expression levels of these key genes and their association with survival. Functional and pathway enrichment analyses on the DEGs were conducted using the Enrichr server. In total, 698 DEGs were identified, consisting of 377 up-regulated genes and 318 down-regulated genes. Within the PPI network, 11 key up-regulated genes and 13 key down-regulated genes associated with GBM were identified. NOTCH1, TOP2A, CD44, PTPRC, CDK4, HNRNPU, and PDGFRA were found to be important targets for potential drug design against GBM. Additionally, functional enrichment analysis revealed the significant impact of Epstein-Barr virus (EBV), Cell Cycle, and P53 signaling pathways on GBM.

摘要

胶质母细胞瘤(GBM)是最常见且侵袭性最强的脑肿瘤类型。它被世界卫生组织归类为IV级肿瘤,即最高级别。总体预后较差,大多数患者仅存活约一年。只有5%的患者存活时间超过5年。了解驱动GBM进展的分子机制对于制定更好的诊断和治疗策略至关重要。确定参与GBM发病机制的关键基因对于全面了解该疾病并开发靶向治疗方法至关重要。在本研究中,从基因表达综合数据库(GEO)获取了两个数据集GSE108474和GSE50161,以比较GBM与正常样本之间的基因表达。鉴定并分析了差异表达基因(DEG)。为构建常见上调和下调基因的蛋白质-蛋白质相互作用(PPI)网络,使用了STRING 11.5和Cytoscape 3.9.1。通过该网络分析确定了关键基因。使用GEPIA数据库确认这些关键基因的表达水平及其与生存的关联。使用Enrichr服务器对DEG进行功能和通路富集分析。总共鉴定出698个DEG,包括377个上调基因和318个下调基因。在PPI网络中,鉴定出11个与GBM相关的关键上调基因和13个关键下调基因。发现NOTCH1、TOP2A、CD44、PTPRC、CDK4、HNRNPU和PDGFRA是针对GBM潜在药物设计的重要靶点。此外,功能富集分析揭示了爱泼斯坦-巴尔病毒(EBV)、细胞周期和P53信号通路对GBM的重大影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dc06/10431734/840c779637d0/KMCO_A_2246657_F0001_OC.jpg

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