Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma

Xinhui WANG; Shanshan JIANG; Bo WU; Ziling LIU

doi:10.16016/j.1000-5404.201812213

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Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma

Basic Medicine | 更新时间：2026-01-09

- Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma
- Journal of Third Military Medical University Vol. 41, Issue 13, Pages: 1253-1260(2019)
- 作者机构：
  
  1.130021 长春，吉林大学：第一医院肿瘤中心肿瘤科
  2.130021 长春，吉林大学：药学院生物医学工程系
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.201812213
  CLC： R394-33;R730.23;R739.41
- Received：27 December 2018，
  
  Revised：2019-02-12，
  
  Published：15 July 2019
- 稿件说明：
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Xinhui WANG, Shanshan JIANG, Bo WU, et al. Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma[J]. Journal of Third Military Medical University, 2019, 41(13): 1253-1260.
DOI：

Xinhui WANG, Shanshan JIANG, Bo WU, et al. Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma[J]. Journal of Third Military Medical University, 2019, 41(13): 1253-1260. DOI： 10.16016/j.1000-5404.201812213.

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(

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

Objective

To screen the core-driving 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.

Methods

The 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 protein-protein 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.

Results

Genes 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 high-risk 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 progression-free survival (PFS) and overall survival (OS) (

0.05).

Conclusion

In this study

TP53

TOP2A

CDK1

PCNA and ACTA2 were selected as the core driver genes of ependymoma. At the same time

we explored the high-risk signaling pathways that cause EPN

and provided new targets for clinical diagnosis and treatment of EPN

which is of great significance.

关键词

Keywords

references

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