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室管膜瘤核心驱动基因及致病高风险信号通路的筛选
Screening of core driver genes and pathogenic high-risk signaling pathways in ependymoma
- 第三军医大学学报 2019年41卷第13期 页码：1253-1260
- 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：
[刘子玲，E-mail：drzilingliu@163.comLIU Ziling, E-mail: drzilingliu@163.com
- 基金信息：
DOI：10.16016/j.1000-5404.201812213
中图分类号： R394-33;R730.23;R739.41收稿：2018-12-27，
修回：2019-02-12，
纸质出版：2019-07-15
- 稿件说明：
移动端阅览
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.
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.
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. DOI： 10.16016/j.1000-5404.201812213.
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
2
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
2
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
2
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
2
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
2
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
2
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
2
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) (
P
<
0.05).
Conclusion
2
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
THORP N, GANDOLA L. Management of ependymoma in children, adolescents and young adults[J]. Clin Oncol (R Coll Radiol), 2019, 31(3): 162-170. DOI:10.1016/j.clon.2018.12.001.
[TSANG D S, MURRAY L, RAMASWAMY V, et al . Craniospinal irradiation as part of Re-irradiation for children with recurrent intracranial ependymoma[J ] . Neuro-oncology, 2018. [Epub ahead of print ] . DOI: 10.1093/neuonc/noy191 http://dx.doi.org/10.1093/neuonc/noy191 ..
HOSOYA T, KAMBE A, NISHIMURA Y, et al . Pediatric case of Li-fraumeni syndrome complicated with supratentorial anaplastic ependymoma[J ] . World Neurosurg, 2018, 120: 125-128. DOI:10.1016/j.wneu.2018.08.203.
[RYU S M, LEE S H, KIM E S, et al . Predicting survival of patients with spinal ependymoma using machine learning algorithms with the SEER database[J ] . World Neurosurg, 2018. [Epub ahead of print ] . DOI: 10.1016/j.wneu.2018.12.091 http://dx.doi.org/10.1016/j.wneu.2018.12.091 ..
ZHANG C Y, PENG L, ZHANG Y Q, et al . The identification of key genes and pathways in hepatocellular carcinoma by bioinformatics analysis of high-throughput data[J ] . Med Oncol, 2017, 34(6): 101. DOI:10.1007/s12032-017-0963-9.
DOMAZET I, PAŠALIĆ I, NEMIR J, et al . Predictors of functional outcome after spinal ependymoma resection[J ] . J Neurosci Rural Pract, 2018, 9(3): 354-358. DOI:10.4103/jnrp.jnrp_56_18.
DONSON A M, AMANI V, WARNER E A, et al . Identification of FDA-approved oncology drugs with selective potency in high-risk childhood ependymoma[J ] . Mol Cancer Ther, 2018, 17(9): 1984-1994. DOI:10.1158/1535-7163.mct-17-1185.
MENG X B, YANG S J, LI Y J, et al . Combination of proteasome and histone deacetylase inhibitors overcomes the impact of gain-of-function p53 mutations[J ] . Dis Markers, 2018, 2018: 1-7. DOI:10.1155/2018/3810108.
QU H J, SU Y, YU L Z, et al . Wild-type p53 regulates OTOP2 transcription through DNA loop alteration of the promoter in colorectal cancer[J ] . FEBS Open Bio, 2019, 9(1): 26-34. DOI:10.1002/2211-5463.12554.
GARIBALDI F, FALCONE E, TRISCIUOGLIO D, et al . Mutant p53 inhibits miRNA biogenesis by interfering with the microprocessor complex[J ] . Oncogene, 2016, 35(29): 3760-3770. DOI:10.1038/onc.2016.51.
HANLI C, CHEN Y C. Targeting EZH2 for cancer therapy: progress and perspective[J]. Curr Protein Pept Sci, 2015, 16(6): 559-570.
KIRK J S, SCHAARSCHUCH K, DALIMOV Z, et al . Top2a identifies and provides epigenetic rationale for novel combination therapeutic strategies for aggressive prostate cancer[J ] . Oncotarget, 2015, 6(5):3136-3146. DOI:10.18632/oncotarget.3077.
LIU R, FAN M, CANDAS D, et al . CDK1-mediated SIRT3 activation enhances mitochondrial function and tumor radioresistance[J ] . Mol Cancer Ther, 2015, 14(9): 2090-2102. DOI:10.1158/1535-7163.MCT-15-0017.
BEDNAREK K, KIWERSKA K, SZAUMKESSEL M, et al . Recurrent CDK1 overexpression in laryngeal squamous cell carcinoma[J ] . Tumour Biol, 2016, 37(8): 11115-11126. DOI:10.1007/s13277-016-4991-4.
LEE H W, PARK Y M, LEE S J, et al . Alpha-smooth muscle actin (ACTA2) is required for metastatic potential of human lung adenocarcinoma[J ] . Clin Cancer Res, 2013, 19(21): 5879-5889. DOI:10.1158/1078-0432.CCR-13-1181.
STRZALKA W, ZIEMIENOWICZ A. Proliferating cell nuclear antigen (PCNA): A key factor in DNA replication and cell cycle regulation[J]. Ann Bot, 2011, 107(7): 1127-1140. DOI:10.1093/aob/mcq243.
WANG G, CAO X, LAI S, et al . PI3K stimulates DNA synthesis and cell-cycle progression via its p55PIK regulatory subunit interaction with PCNA[J ] . Mol Cancer Ther, 2013, 12(10): 2100-2109. DOI:10.1158/1535-7163.mct-12-0920..
GU L, SMITH S, LI C, et al . A PCNA-derived cell permeable peptide selectively inhibits neuroblastoma cell growth[J ] . PLoS ONE, 2014, 9(4): e94773. DOI:10.1371/journal.pone.0094773.
HERMANSON D J, MARNETT L J. Cannabinoids, endo-cannabinoids, and cancer[J]. Cancer Metastasis Rev, 2011, 30(3/4): 599-612. DOI:10.1007/s10555-011-9318-8.
PIOMELLI D. The molecular logic of endocannabinoid signalling[J]. Nat Rev Neurosci, 2003, 4(11): 873-884. DOI:10.1038/nrn1247.
ZHANG Q Y, ZHANG M, CAO Y. Exposure to morphine affects the expression of endocannabinoid receptors and immune functions[J]. J Neuroimmunol, 2012, 247(1/2): 52-58. DOI:10.1016/j.jneuroim.2012.04.003.
ABIRIA S A, WILLIAMS T V, MUNDEN A L, et al . Expression of Hedgehog ligand and signal transduction components in mutually distinct isocitrate dehydrogenase mutant glioma cells supports a role for paracrine signaling[J ] . J Neurooncol, 2014, 119(2): 243-251. DOI:10.1007/s11060-014-1481-7.
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