丙戊酸钠抗癫痫疗效相关枢纽基因鉴定

Identification of hub genes in response to valproate treatment in patients with epilepsy

目的采用加权基因共表达网络分析探索抗癫痫药物丙戊酸钠疗效相关的基因模块及核心枢纽基因。方法从GEO数据库下载表达谱数据,构建基因共表达网络;采用Pearson相关性检验筛选与抗癫痫药物丙戊酸钠疗效显著相关的基因模块,根据模块内的连接性筛选枢纽基因;利用GO功能富集分析和KEGG通路分析对模块进行功能注释。结果根据基因表达的相关性,共构建了12个基因共表达模块,其中分别选出与是否采取丙戊酸钠药物治疗表型明显相关(r=0.57,P<0.0001)和与丙戊酸钠治疗是否有效表型显著相关(r=-0.53,P<0.0001)的两个基因模块;发现包含S1PR5、SARM1等基因以及MAGED1、FBXO31等基因分别在两个模块中处于核心地位;通过生物注释功能发现,两个模块中的基因主要富集在免疫调控、MAPK通路等生物学过程中。结论丙戊酸钠用药引起癫痫患者体内免疫和代谢通路变化,其疗效是否显著可能与MAGED1、FBXO31等基因功能相关。

Aim To investigate the hub genes associated with response to valproate treatment in patients with epilepsy by using weighted gene co-expression network analysis.Methods We downloaded data from the GEO database and constructed the gene co-expression network.Pearson correlation test was used to calculate the correlation between module genes and clinical traits,to screen gene modules significantly associated with response to valproate treatment,and to screen hub genes according to the connectivity within modules.GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the modules.Results A total of 12 gene co-expression modules were constructed from the correlations of gene expression,in which the yellow module was significantly correlated with the drug treatment(r=0.57,P<0.0001)and the blue module was significantly correlated with the response to valproate(r=-0.53,P<0.0001).We found that S1PR5,SARM1 and MAGED1,FBXO31 were in the hub of the co-expression network.The biological annotation function revealed that the genes in both modules were mainly enriched in immune response and MPAK pathways.Conclusions Our work delivers preliminary data that valproate treatment causes the changes of immune and metabolic pathways in patients,and the response to epilepsy may be related to the expression of MAGED1,FBXO31.