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用于绘制卵巢癌潜在新基因和相关通路图谱的整合生物信息学方法

Integrative Bioinformatics Approaches to Map Potential Novel Genes and Pathways Involved in Ovarian Cancer.

作者信息

Kumar S Udhaya, Kumar D Thirumal, Siva R, Doss C George Priya, Zayed Hatem

机构信息

School of Biosciences and Technology, Vellore Institute of Technology, Vellore, India.

Department of Biomedical Sciences, College of Health and Sciences, Qatar University, Doha, Qatar.

出版信息

Front Bioeng Biotechnol. 2019 Dec 17;7:391. doi: 10.3389/fbioe.2019.00391. eCollection 2019.

Abstract

Ovarian cancer (OC) is the seventh most commonly detected cancer among women. This study aimed to map the hub and core genes and potential pathways that might be involved in the molecular pathogenesis of OC. In the present work, we analyzed a microarray dataset (GSE126519) from the Gene Expression Omnibus (GEO) database and used the GEO2R tool to screen OC cells and ovarian SINE-resistant cancer cells for differentially expressed genes (DEGs). For the functional annotation of the DEGs, we conducted Gene Ontology (GO) and pathway enrichment analyses (KEGG) using the DAVID v6.8 online server and GenoGo Metacore™, Cortellis Solution software. Protein-protein interaction (PPI) networks were constructed using the STRING database, and Cytoscape software was used for visualization. The survival analysis was performed using the online platform GEPIA2 to determine the prognostic value of the expression of hub genes in cell lines from OC patients. We identified a total of 809 upregulated and 700 downregulated DEGs. GO analysis revealed that the genes with statistically significant differences in expression were mainly associated with biological processes involved in the cell cycle, the mitotic cell cycle, mitotic nuclear division, organ morphogenesis, cell development, and cell morphogenesis. By using the Analyze Networks (AN) algorithm in GeneGo, we identified the most relevant biological networks involving DEGs that were mainly enriched in the cell cycle (in metaphase checkpoints) and revealed the role of APC in cell cycle regulation pathways. We found 10 hub genes and four core genes (, and ) that are strongly linked to OC. This study sheds light on the molecular pathogenesis of OC and is expected to provide potential molecular biomarkers that are beneficial for the treatment and clinical molecular diagnosis of OC.

摘要

卵巢癌(OC)是女性中第七大最常被检测出的癌症。本研究旨在绘制可能参与OC分子发病机制的枢纽基因、核心基因及潜在通路。在本研究中,我们分析了来自基因表达综合数据库(GEO)的一个微阵列数据集(GSE126519),并使用GEO2R工具筛选OC细胞和卵巢SINE抗性癌细胞中的差异表达基因(DEG)。对于DEG的功能注释,我们使用DAVID v6.8在线服务器以及GenoGo Metacore™、Cortellis Solution软件进行基因本体论(GO)和通路富集分析(KEGG)。使用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并使用Cytoscape软件进行可视化。使用在线平台GEPIA2进行生存分析,以确定枢纽基因在OC患者细胞系中的表达的预后价值。我们共鉴定出809个上调的DEG和700个下调的DEG。GO分析表明,表达具有统计学显著差异的基因主要与细胞周期、有丝分裂细胞周期、有丝分裂核分裂、器官形态发生、细胞发育和细胞形态发生等生物学过程相关。通过在GeneGo中使用分析网络(AN)算法,我们确定了涉及DEG的最相关生物学网络,这些网络主要富集在细胞周期(中期检查点),并揭示了APC在细胞周期调控通路中的作用。我们发现了10个枢纽基因和4个核心基因(、和)与OC密切相关。本研究揭示了OC的分子发病机制,有望提供对OC治疗和临床分子诊断有益的潜在分子生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef3f/6927934/e8595ae2ca2b/fbioe-07-00391-g0001.jpg

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