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通过综合生物信息学分析鉴定 EphA2 和 RMI2 为宫颈鳞癌的两个新的关键基因。

Identification of EPHX2 and RMI2 as two novel key genes in cervical squamous cell carcinoma by an integrated bioinformatic analysis.

机构信息

Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

J Cell Physiol. 2019 Nov;234(11):21260-21273. doi: 10.1002/jcp.28731. Epub 2019 Apr 30.

Abstract

Cervical cancer is the fourth most common malignancy in women worldwide and cervical squamous cell carcinoma (CESC) is the most common histological type of cervical cancer. The dysregulation of genes plays a significant role in cancer. In the present study, we screened out differentially expressed genes (DEGs) of CESC in the GSE63514 data set from the Gene Expression Omnibus database. An integrated bioinformatics analysis was used to select hub genes, as well as to investigate their related prognostic signature, functional annotation, methylation mechanism, and candidate molecular drugs. As a result, a total of 1907 DEGs were identified (944 were upregulated and 963 were downregulated). In the protein-protein interaction network, three hub modules and 30 hub genes were identified. And two hub modules and 116 hub genes were screened out from four CESC-related modules by the weighted gene coexpression network analysis. The gene ontology term enrichment analysis and Kyoto encyclopedia of genes and genomes pathway analysis were performed to better understand functions and pathways. Genes with a significant prognostic value were found by prognostic signature analysis. And there were five genes (EPHX2, CHAF1B, KIAA1524, CDC45, and RMI2) identified as significant CESC-associated genes after expression validation and survival analysis. Among them, EPHX2 and RMI2 were noted as two novel key genes for the CESC-associated methylation and expression. In addition, four candidate small molecule drugs for CESC (camptothecin, resveratrol, vorinostat, and trichostatin A) were defined. Further studies are required to explore these significant CESC-associated genes for their potentiality in diagnosis, prognosis, and targeted therapy.

摘要

宫颈癌是全球女性中第四常见的恶性肿瘤,宫颈鳞状细胞癌(CESC)是最常见的宫颈癌组织学类型。基因失调在癌症中起着重要作用。在本研究中,我们从基因表达综合数据库中筛选出 GSE63514 数据集的 CESC 差异表达基因(DEGs)。采用综合生物信息学分析方法选择枢纽基因,并研究其相关的预后特征、功能注释、甲基化机制和候选分子药物。结果共鉴定出 1907 个 DEGs(944 个上调,963 个下调)。在蛋白质-蛋白质相互作用网络中,确定了三个枢纽模块和 30 个枢纽基因。通过加权基因共表达网络分析,从四个与 CESC 相关的模块中筛选出两个枢纽模块和 116 个枢纽基因。进行基因本体论术语富集分析和京都基因与基因组百科全书通路分析,以更好地理解功能和通路。通过预后特征分析找到了具有显著预后价值的基因。通过表达验证和生存分析,确定了五个与 CESC 显著相关的基因(EPHX2、CHAF1B、KIAA1524、CDC45 和 RMI2)。其中,EPHX2 和 RMI2 被认为是与 CESC 相关的甲基化和表达的两个新的关键基因。此外,还确定了四种用于 CESC 的候选小分子药物(喜树碱、白藜芦醇、伏立诺他和曲古抑菌素 A)。需要进一步研究这些与 CESC 显著相关的基因,以探索其在诊断、预后和靶向治疗方面的潜力。

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