目的 比较肌萎缩侧索硬化的两种不同基因突变型(C9orf72与CHMP2B)表达谱差异来探讨该类疾病可能的发病机制及治疗靶点。方法 从GEO数据库中下载C9orf72基因突变肌萎缩侧索硬化数据集(GSE68605)及CHMP2B基因突变肌萎缩侧索硬化数据集(GSE19332)。使用R软件(3.5.0版本)、Cytoscape 3.6.1软件及在线工具(DAVID及STRING)进行数据分析。结果 从两个数据集中,获得了11个样本,其中8个为C9orf72基因突变,3个为CHMP2B基因。发现了13个差异表达基因,在GO及KEGG功能富集分析中发现仅有CALM1-3及RYR2富集在钙离子检测、通过钙离子释放的调节影响心肌的收缩功能等。其中钙调蛋白是引起C9orf72基因突变肌萎缩侧索硬化及CHMP2B基因突变肌萎缩侧索硬化差异的关键蛋白。结论 CALM基因在C9orf72基因突变肌萎缩侧索硬化患者中高表达,钙调蛋白可能是诊断及治疗C9orf72基因突变肌萎缩侧索硬化患者的重要靶点。
Abstract
Objective To compare the difference of gene expressions between C9orf72 mutation ALS and CHMP2B mutation ALS.Methods Datasets (GSE68605 and GSE19332) were acquired from the gene expression omnibus (GEO) database. R software (version 3.5.0), Cytoscape 3.6.1 software and online tool DAVID and STRING were used for data analysis.Results A total of eleven independent samples (eight samples of C9orf72 mutation ALS and three samples of CHMP2B mutation ALS) were analyzed. Thirteen differentially expressed genes (DEGs) were identified in the cervical spinal cord motor neurons of the two distinct ALS variants. It was found that only CALM2, CALM1, CALM3 and RYR2 were classified during GO and KEEG functional enrichment, and that CALM1, CALM2 and CALM3 were outstanding in the Hub protein analysis.Conclusions The expression of CALM genes is up-regulated in the C9orf72 mutation ALS. Calmodulin might be a potential biomarker for ALS diagnosis and effective target for ALS treatment.
关键词
肌萎缩侧索硬化 /
C9orf72 /
CHMP2B /
CALM /
钙调蛋白
Key words
amyotrophic lateral sclerosis /
C9orf72 /
CHMP2B /
CALM /
calmodulin
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