【摘 要】
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Background: Valproic acid(VPA),an old antiepileptic drug,is advised as the first line therapy for absent epilepsy.However,approximately one-third of patients are still refractory to epilepsy even trea
【机 构】
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Children's Hospital of Fudan University,Shanghai 201102
【出 处】
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第二十九届全国儿科药学学术年会暨第十届全国儿科药学中青年药师论文报告会
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Background: Valproic acid(VPA),an old antiepileptic drug,is advised as the first line therapy for absent epilepsy.However,approximately one-third of patients are still refractory to epilepsy even treated by VPA.While patients who are resistant to VPA have a specificity of 100%to identify as drug resistance.In this study,the transcriptome expression between VPA responsive and non-responsive patients was analyzed to explore the biomarkers for predicting the efficacy of VPA.Material/Methods: RNA-seq analysis was applied to detect the transcriptome expression,while differential expression genes(DEGs)were analyzed by Cuffdiff software,function of DEGs was enriched by DAVID,Protein-protein interaction network was clustered by STRING and visualized by Cytoscape.Results: A total of 389 differential genes were found between VPA-responsive and non-responsive pediatrics,of which 227 genes were upregulated,162 genes were downregulated.Upregulated DEGs were enriched in cytokine activity,chemokine activity,and chemokine receptor binding,while downregulated genes were in cation channel activity,iron ion binding,and IgE receptor activity.In addition,toll-like receptor signaling pathway,pathway in cancer,and cytokine-cytokine receptor interaction were the most concentrated pathways.Three modules were found by protein-protein interaction analysis,while,genes of CCL3,CCL4,CXCL9,IL-1,and TNF which closely related to epilepsy may be the potential hub genes.Conclusions: Chemokines genes(CCL3,CCL4,CXCL9,IL-1,and TNF)may participate in the process of VPA resistance,which may also be the potential biomarkers for predicting the efficacy of VPAbut need to be verified.
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