[1]王新慧,姜姗姗,武波,等.室管膜瘤核心驱动基因及致病高风险信号通路的筛选[J].第三军医大学学报,2019,41(13):1253-1260.
 WANG Xinhui,JIANG Shanshan,WU Bo,et al.Screening of core driver genes and pathogenic highrisk signaling pathways in ependymoma[J].J Third Mil Med Univ,2019,41(13):1253-1260.
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
41卷
期数:
2019年第13期
页码:
1253-1260
栏目:
基础医学
出版日期:
2019-07-15

文章信息/Info

Title:
Screening of core driver genes and pathogenic highrisk signaling pathways in ependymoma
作者:
王新慧姜姗姗武波刘子玲
长春,吉林大学:第一医院肿瘤中心肿瘤科1,药学院生物医学工程系2
Author(s):
WANG Xinhui1 JIANG Shanshan2 WU Bo1 LIU Ziling1

1Department of Oncology, Cancer Center, First Hospital of Jilin University, 2Department of Biomedical Engineering, School of Pharmacy, Jilin University, Changchun, Jilin Province, 130021, China

关键词:
室管膜瘤核心驱动基因肿瘤分子靶向治疗
Keywords:
ependymoma driver genes tumor molecular targeting therapy
分类号:
R39433; R730.23; R739.41
文献标志码:
A
摘要:

目的筛选影响室管膜瘤(ependymoma,EPN)发生、发展的核心驱动致病基因,探讨其涉及的具体致病信号通路,同时阐明患者预后情况与驱动基因表达水平的关系。方法利用基因芯片技术,基于微阵列芯片数据分析,采用生物学信息分析方法,筛选出室管膜瘤与正常脑组织的差异表达基因。通过GO(基因本体论)、KEGG(京都基因和基因组百科全书)信号通路分析以及PPI蛋白互作网络的构建,筛选出差异表达基因及其主要富集的信号通路,明确核心致病高风险因子。此外,对CGGA临床样本网站收集的325例室管膜瘤患者的临床样本数据进行生存分析,明确核心基因表达水平与患者预后的关系。结果TP53、TOP2A、CDK1、PCNA和ACTA2是室管膜瘤核心驱动基因,其异常表达促进室管膜瘤的发生、发展。Hedgehog信号通路、Notch信号通路以及错配修复信号通路是室管膜瘤发生、发展的高风险信号通路。TOP2A、CDK1、PCNA和ACTA2表达量相对较低的室管膜瘤患者预后良好,其PFS(无进展生存期)和OS(总生存期)时间更长(P<0.05)。 结论本研究筛选出室管膜瘤的核心驱动致病基因:TP53、TOP2A、CDK1、PCNA和ACTA2。致EPN发生的高风险信号通路有:Hedgehog信号通路、Notch信号通路以及错配修复信号通路。

Abstract:

ObjectiveTo screen the coredriving pathogenic genes in the occurrence and development of ependymoma (EPN), explore the involved signal pathways of its pathogenesis, and to clarify the relationship of prognosis with expression of these driver genes.  MethodsThe differentially expressed gene (DEGs) were identified after comparing between gene expression profiles of the EPN tissues and normal tissues based on gene chip, microarray and bioinformatics. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and proteinprotein interaction (PPI) network analyses were conducted to find out the enrichment functions, pathways and hub genes. After hub genes were identified, the survival analysis of 325 patients, which data obtained from Chinese Glioma Genome Atlas (CCGA), were performed to clarify the relationship between prognosis and the expression levels of the hub genes.  ResultsGenes TP53, TOP2A, CDK1, PCNA and ACTA2 were found as core driver genes, and their aberrant expression promoted the occurrence and development of EPN; Hedgehog signaling pathway, Notch signal pathway and mismatch repair signal pathway were the highrisk signal pathways for the development of EPN. And the results of survival analysis showed that the patients with lower expression of TOP2A, CDK1, PCNA and ACTA2 had favorable prognosis and longer progressionfree survival (PFS) and overall survival (OS) (P<0.05).  ConclusionIn this study, TP53, TOP2A, CDK1, PCNA and ACTA2 were selected as the core driver genes of ependymoma. At the same time, we explored the highrisk signaling pathways that cause EPN, and provided new targets for clinical diagnosis and treatment of EPN, which is of great significance.

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更新日期/Last Update: 2019-07-08