PDF(944 KB)
生物信息学分析影响胶质母细胞瘤生物学行为的关键基因
何心, 秦至臻, 李鑫, 赵水强, 程诚, 王震, 封耀辉, 邱险峻, 杨书芹, 王建祯
武警医学 ›› 2020, Vol. 31 ›› Issue (4) : 328-331.
PDF(944 KB)

PDF(944 KB)
生物信息学分析影响胶质母细胞瘤生物学行为的关键基因
Identification of biological behavior HUB genes of glioblastoma by bioinformatics
目的 应用生物信息学方法分析与胶质母细胞瘤(glioblastoma,GBM)生物学行为密切相关的关键(HUB)基因。方法 在基因表达综合数据库(gene expression omnibus, GEO)中获取GBM相关芯片数据,并利用R语言分析GBM组织与正常脑组织之间的差异表达基因;利用GO 数据库和 KEGG数据库对差异表达基因进行功能富集和注释;利用 STRING 数据库和 Cytoscape 软件构建蛋白质相互作用网络(protein-protein interaction, PPI),分析HUB基因;利用TCGA数据库分析HUB基因对胶质瘤患者预后的影响。结果 共鉴定出 628个差异表达基因,其中 87个为上调基因,541个为下调基因。生物学过程主要富集在神经递质分泌、胞外分泌的监管、化学突触传递等方面。通过不同算法的比较,最终得到19个HUB基因,HUB基因主要富集的信号通路包括逆行神经的信号通路、突触囊泡循环通路及GABA相关通路等。在HUB基因中GABRD基因表达情况与肿瘤预后显著相关。结论 DNM1、RBFOX1、GABRD等HUB基因可能在GBM的生物学过程中发挥重要作用。
Objective To analyze the chip data of multigroup glioblastoma (GBM) gene expression profiles in GEO database using bioinformatics, and to find the HUB genes closely related to the biological behavior of GBM.Methods GBM-related datasets were obtained from the GEO database, and the differentially expressed genes between GBM and normal brain tissue were analyzed via the R language. GO and KEGG databases were used for functional enrichment and functional annotation of differentially expressed genes. STRING database and Cytoscape software were used to construct protein-protein interaction (PPI) to analyze HUB genes, while TCGA database was used to analyze the survival of HUB genes.Results A total of 628 differentially expressed genes were identified, including 87 up-regulated genes and 541 down-regulated ones. Biological processes were concentrated in neurotransmitter secretion, extracellular secretion regulation and chemical synaptic transmission. Through the comparison of different algorithms, 19 HUB genes were finally obtained. The main signal pathways enriched by HUB genes included the signal pathways of retrograde nerves, synaptic vesicular circulation pathways and gaba-related pathways. The expression of GABRD genes was significantly correlated with tumor prognosis.Conclusions The differentially expressed genes found in this study can shed light on the molecular mechanism of GBM, and the HUB genes can be the focus of further research.
胶质母细胞瘤 / 差异表达基因 / 生物信息学分析 / 关键基因
GBM / differentially expressed gene / bioinformatics analysis / HUB gene
[1] Zhang Y, Xu J, Zhu X. A 63 signature genes prediction system is effective for glioblastoma prognosis[J]. Int J Mol Med, 2018,41(4):2070-2078.
[2] Sun S, Wang Y, Wu Y, et al. Identification of COL1A1 as an invasion related gene in malignant astrocytoma[J]. Int J Oncol, 2018,53(6):2542-2554.
[3] Geng R X, Li N, Xu Y, et al. Identification of Core Biomarkers Associated with Outcome in Glioma: Evidence from Bioinformatics Analysis[J]. Dis Markers, 2018,2018:3215958.
[4] Phillips H S, Kharbanda S, Chen R, et al. Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis[J]. Cancer Cell, 2006,9(3):157-173.
[5] Goossens N, Nakagawa S, Sun X, et al. Cancer biomarker discovery and validation[J]. Transl Cancer Res, 2015,4(3):256-269.
[6] Diamandis P, Aldape K D. Insights from molecular profiling of adult glioma[J]. J Clin Oncol, 2017,35(21):2386-2393.
[7] Louis D N, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary[J]. Acta Neuropathol, 2016,131(6):803-20.
[8] Corroyer D A, Pérès E A, Petit E, et al. Detection of glioblastoma response to temozolomide combined with bevacizumab based on μMRI and μPET imaging reveals [18F]-fluoro-L-thymidine as an early and robust predictive marker for treatment efficacy[J]. Neuro Oncol, 2013,15(1):41-56.
[9] Szopa W, Burley T A, Kramer M G, et al. Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives[J]. Biomed Res Int, 2017,2017:8013575.
[10] Karsy M, Neil J A, Guan J, et al. A practical review of prognostic correlations of molecular biomarkers in glioblastoma[J]. Neurosurg Focus, 2015,38(3):E4.
[11] Dai Z, Wu J, Chen F, et al. CXCL5 promotes the proliferation and migration of glioma cells in autocrine- and paracrine-dependent manners[J]. Oncol Rep, 2016,36(6):3303-3310.
[12] Caccavale J, Fiumara D, Stapf M, et al. A simple and accurate rule-based modeling framework for simulation of autocrine/paracrine stimulation of glioblastoma cell motility and proliferation by L1CAM in 2-D culture[J]. BMC Syst Biol, 2017,11(1):124.
[13] Silginer M, Nagy S, Happold C, et al. Autocrine activation of the IFN signaling pathway may promote immune escape in glioblastoma[J]. Neuro Oncol, 2017,19(10):1338-1349.
[14] Fujita M, Yamamoto T, Iyoda T, et al. Autocrine production of PDGF stimulated by the tenascin-c-derived Peptide TNIIIA2 Induces hyper-proliferation in glioblastoma Cells[J]. Int J Mol Sci, 2019,20(13).
[15] Patel V N, Gokulrangan G, Chowdhury S A, et al. Network signatures of survival in glioblastoma multiforme[J]. PLoS Comput Biol, 2013,9(9):e1003237.
[16] Gross A M, Kreisberg J F, Ideker T. Analysis of matched tumor and normal profiles reveals common transcriptional and epigenetic signals shared across cancer types[J]. PLoS One, 2015,10(11):e0142618.
[17] Wang Y, Gray D R, Robbins A K, et al. Subphenotype meta-analysis of testicular cancer genome-wide association study data suggests a role for RBFOX family genes in cryptorchidism susceptibility[J]. Hum Reprod, 2018,33(5):967-977.
[18] Faisal M, Büsche G, Schlue J, et al. RNA-binding protein (RBFOX1) inherited polymorphism rs8051518 is not associated with splice factor mutations in myelodysplastic syndromes and myeloproliferative neoplasms[J]. Ann Hematol, 2019,98(5):1297-1299.
[19] Hujber Z, Horváth G, Petövári G, et al. GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas[J]. J Exp Clin Cancer Res, 2018,37(1):271.
[20] El-Habr E A, Dubois L G, Burel V F, et al. A driver role for GABA metabolism in controlling stem and proliferative cell state through GHB production in glioma[J]. Acta Neuropathol, 2017,133(4):645-660.
/
| 〈 |
|
〉 |