Identification of differentially expressed genes in peripheral blood of patients with idiopathic epilepsy by bioinformatics analysis_Journal of Epilepsy

Authors：

 ZHANG Yingchun ¹ , HE Chengcheng ² , DUAN Xiping ³

1. Department of Neurology, People’s Hospital of Zhongjiang, Deyang 618100, China;
2. Emergency Department, People’s Hospital of Zhongjiang, Deyang 618100, China;
3. Grade 2017, College of Acupuncture and Massage, Chengdu University of Traditional Chinese Medicine, Chengdu 610032, China;

Corresponding author：

ZHANG Yingchun, Email: 2447198164@qq.com

Keywords：

Idiopathic epilepsy; Differentially expressed genes; Hub genes; Protein-protein interaction network; Enrichment analysis

DOI：

10.7507/2096-0247.20200082

Video：

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Objective To investigate key differentially expressed genes (DEGs) in peripheral blood of idiopathic epilepsy patients, as well as their biological functions, cellular localization, involved signaling pathways, through bioinformatics analysis. So to provide new insights for the pathogenesis and prevention of idiopathic epilepsy.Methods Firstly, we screened and downloaded microarray data including 6 peripheral blood samples of drug-naive patients with idiopathic epilepsy, 8 peripheral blood samples of responders of idiopathic epilepsy treated with Valproate (VPA), and 10 peripheral blood samples of non-responders of idiopathic epilepsy treated with VPA from Gene Expression Omnibus (GEO) data series GSE143272, which Public in January 2020. Secondly, we identified DEGs via the limma package and others in R software. Then we had gotten 74 DEGs, and subsequently conducted gene ontology and pathway enrichment analysis, PPI network analysis and hub gene analysis, using multiple methods containing DAVID, STRING, and Cytohubba in Cytoscape.Results We had identified significant hub DEGs, including TREML3P, KCNJ15, ORM1, RNA28S5, ELANE, RETN, ARG1, LCN2, SLPI, HP, PGLYRP1, BPI, DEFA4, TCN1, MPO, MMP9, CTSG, CXCL8, RNASE3, RNASE2, S100A12, DEFA1B, DEFA1, DEFA3, CEACAM8, MS4A3, PTGS2, PI3, CCL3. The biological processes involved in these DEGs include immune response, inflammatory response, chemotaxis, etc. While, the molecular function is focused on peroxidase activity, chemokine activity, etc. Moreover, KEGG pathway enrichment analysis shows that DEGs were mainly involved in cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, chemokine signaling pathway and so on.Conclusion These important key DEGs may be involved in the onset and development of idiopathic epilepsy through a variety of signaling pathways and complex mechanisms.

Citation： ZHANG Yingchun, HE Chengcheng, DUAN Xiping. Identification of differentially expressed genes in peripheral blood of patients with idiopathic epilepsy by bioinformatics analysis. Journal of Epilepsy, 2020, 6(6): 498-506. doi: 10.7507/2096-0247.20200082 Copy

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14.	Toscano ECB, Lessa JMK, Goncalves AP, et al. Circulating levels of adipokines are altered in patients with temporal lobe epilepsy. Epilepsy Behav, 2019, 90: 137-141.
15.	Sonmez FM, Zaman D, Aksoy A, et al. The effects of topiramate and valproate therapy on insulin, c-peptide, leptin, neuropeptide y, adiponectin, visfatin, and resistin levels in children with epilepsy. Seizure, 2013, 22(10): 856-861.
16.	Gloria-Bottini F, Lucarelli P, Saccucci P, et al. Genetic polymorphism and idiopathic generalized epilepsy. Evidence of interaction between haptoglobin and acp1 systems. Neuropediatrics, 2008, 39(6): 357-358.
17.	Sadrzadeh SM, Saffari Y, Bozorgmehr J. Haptoglobin phenotypes in epilepsy. Clin Chem, 2004, 50(6): 1095-1097.
18.	Tannich F, Tlili A, Pintard C, et al. Activation of the phagocyte nadph oxidase/nox2 and myeloperoxidase in the mouse brain during pilocarpine-induced temporal lobe epilepsy and inhibition by ketamine. Inflammopharmacology, 2020, 28(2): 487-497.
19.	Eastman CL, D'Ambrosio R, Ganesh T. Modulating neuroinflammation and oxidative stress to prevent epilepsy and improve outcomes after traumatic brain injury. Neuropharmacology, 2020, 172: 107907.
20.	Ruber T, David B, Luchters G, et al. Evidence for peri-ictal blood-brain barrier dysfunction in patients with epilepsy. Brain, 2018, 141(10): 2952-2965.
21.	Meguid NA, Samir H, Bjorklund G, et al. Altered s100 calcium-binding protein b and matrix metallopeptidase 9 as biomarkers of mesial temporal lobe epilepsy with hippocampus sclerosis. J Mol Neurosci, 2018, 66(4): 482-491.
22.	Simoes PSR, Zanelatto AO, Assis MC, et al. Plasma kallikrein-kin in system contributes to peripheral inflammation in temporal lobe epilepsy. J Neurochem, 2019, 150(3): 296-311.
23.	de Vries EE, van den Munckhof B, Braun KP, et al. Inflammatory mediators in human epilepsy: A systematic review and meta-analysis. Neurosci Biobehav Rev, 2016, 63: 177-190.
24.	Cerri C, Caleo M, Bozzi Y. Chemokines as new inflammatory players in the pathogenesis of epilepsy. Epilepsy Res, 2017, 136: 77-83.
25.	van Gassen KL, de Wit M, Koerkamp MJ, et al. Possible role of the innate immunity in temporal lobe epilepsy. Epilepsia, 2008, 49(6): 1055-1065.
26.	Sanz P, Garcia-Gimeno MA. Reactive glia inflammatory signaling pathways and epilepsy. Int J Mol Sci, 2020, 21(11): 4096.

1. Thijs RD, Surges R, O'Brien TJ, et al. Epilepsy in adults. Lancet, 2019, 393(10172): 689-701.
2. 吴江主编. 神经病学 (第 2 版). 北京: 人民卫生出版社, 2010: 282-308.
3. 蒋永莉, 杨西爱, 杨颖, 等. 癫痫遗传学研究新进展. 中华神经科杂志, 2017, 50(6): 470-473.
4. 洪震. 丙戊酸钠——癫痫治疗一线用药. 癫痫杂志, 2017, 3(3): 278-279.
5. Rawat C, Kushwaha S, Srivastava AK, et al. Peripheral blood gene expression signatures associated with epilepsy and its etiologic classification. Genomics, 2020, 112(1): 218-224.
6. Rawat C, Kutum R, Kukal S, et al. Down regulation of peripheral ptgs2/cox-2 in response to valproate treatment in patients with epilepsy. Sci Rep, 2020, 10(1): 2546.
7. Ritchie ME, Phipson B, Wu D, et al. Limma powers differential expression analyses for rna-sequencing and microarray studies. Nucleic Acids Res, 2015, 43(7): e47.
8. Huang da W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using david bioinformatics resources. Nat Protoc, 2009, 4(1): 44-57.
9. Huang da W, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: Paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res, 2009, 37(1): 1-13.
10. Szklarczyk D, Morris JH, Cook H, et al. The string database in 2017: Quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res, 2017, 45(D1): D362-D368.
11. Chin CH, Chen SH, Wu HH, et al. Cytohubba: Identifying hub objects and sub-networks from complex interactome. BMC Syst Biol, 2014, 8(Suppl 4): S11.
12. Pantazis AA-O, Kaneko MA-O, Angelini M, et al. Tracking the motion of k(v) 1.2 voltage sensor reveals the molecular perturbations caused by a de novo mutation in a case of epilepsy. Lid-10.1113/jp280438 [doi]. 1469-7793 (Electronic).
13. Paulhus K, Ammerman L, Glasscock E. Clinical spectrum of kcna1 mutations: New insights into episodic ataxia and epilepsy comorbidity. Int J Mol Sci, 2020, 21(8): 2802.
14. Toscano ECB, Lessa JMK, Goncalves AP, et al. Circulating levels of adipokines are altered in patients with temporal lobe epilepsy. Epilepsy Behav, 2019, 90: 137-141.
15. Sonmez FM, Zaman D, Aksoy A, et al. The effects of topiramate and valproate therapy on insulin, c-peptide, leptin, neuropeptide y, adiponectin, visfatin, and resistin levels in children with epilepsy. Seizure, 2013, 22(10): 856-861.
16. Gloria-Bottini F, Lucarelli P, Saccucci P, et al. Genetic polymorphism and idiopathic generalized epilepsy. Evidence of interaction between haptoglobin and acp1 systems. Neuropediatrics, 2008, 39(6): 357-358.
17. Sadrzadeh SM, Saffari Y, Bozorgmehr J. Haptoglobin phenotypes in epilepsy. Clin Chem, 2004, 50(6): 1095-1097.
18. Tannich F, Tlili A, Pintard C, et al. Activation of the phagocyte nadph oxidase/nox2 and myeloperoxidase in the mouse brain during pilocarpine-induced temporal lobe epilepsy and inhibition by ketamine. Inflammopharmacology, 2020, 28(2): 487-497.
19. Eastman CL, D'Ambrosio R, Ganesh T. Modulating neuroinflammation and oxidative stress to prevent epilepsy and improve outcomes after traumatic brain injury. Neuropharmacology, 2020, 172: 107907.
20. Ruber T, David B, Luchters G, et al. Evidence for peri-ictal blood-brain barrier dysfunction in patients with epilepsy. Brain, 2018, 141(10): 2952-2965.
21. Meguid NA, Samir H, Bjorklund G, et al. Altered s100 calcium-binding protein b and matrix metallopeptidase 9 as biomarkers of mesial temporal lobe epilepsy with hippocampus sclerosis. J Mol Neurosci, 2018, 66(4): 482-491.
22. Simoes PSR, Zanelatto AO, Assis MC, et al. Plasma kallikrein-kin in system contributes to peripheral inflammation in temporal lobe epilepsy. J Neurochem, 2019, 150(3): 296-311.
23. de Vries EE, van den Munckhof B, Braun KP, et al. Inflammatory mediators in human epilepsy: A systematic review and meta-analysis. Neurosci Biobehav Rev, 2016, 63: 177-190.
24. Cerri C, Caleo M, Bozzi Y. Chemokines as new inflammatory players in the pathogenesis of epilepsy. Epilepsy Res, 2017, 136: 77-83.
25. van Gassen KL, de Wit M, Koerkamp MJ, et al. Possible role of the innate immunity in temporal lobe epilepsy. Epilepsia, 2008, 49(6): 1055-1065.
26. Sanz P, Garcia-Gimeno MA. Reactive glia inflammatory signaling pathways and epilepsy. Int J Mol Sci, 2020, 21(11): 4096.

Journal of Epilepsy

Identification of differentially expressed genes in peripheral blood of patients with idiopathic epilepsy by bioinformatics analysis

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