帕金森病和抑郁症患者脑组织Brodman9区域共同差异基因的生物信息学分析

Common Differential Genes in the Brodman9 Region of Brain Tissues in Patients with Parkinson's Disease and Major Depression Disease:A Bioinformatics-Based Study

目的:比较分析帕金森病(Parkinson Disease,PD)和抑郁症(Major depression disease,MDD)在脑组织Brodman9(BA9)区域共同的差异基因(Differential genes,DEGs)、共同通路和关键基因,为PD和MDD共同发病机制研究提供参考。方法:下载GEO数据库中GSE20168、GSE54567、GSE54568和GSE54570芯片数据,使用R语言调取limma,clusterProfiler,ggplot2等生信分析包,以P<0.05并logFC绝对值≥0.3作为标准,分析PD和MDD共表达差异基因,进一步通过GO和KEGG富集分析共同通路,并利用String数据库及cytoscape软件进行蛋白-蛋白相互作用(PPI)网络和关键基因鉴定。结果:PD和MDD患者BA9区域存在34个共同的DEGs,上调21个,分别为:SLC35E1、ATP8B1、TSR1、ZNF721、RIOK3、FBXW12、ZNF160、POLR1B、CACNA1I、MZT2B、PGF、RP11-403P17.4、RPL23AP32、DBT、PRR11、USP34、LRRFIP1、DSERG1、DIP2A、AEBP1和DNAJB2基因,下调13个,分别为NPTX2、PCSK1、SST、PPP1CB、SEC22B、ENPP4、NME5、CAPZA2、GLRB、ITFG1、GLIPR1、TM6SF1和DUSP6基因;DEGs功能富集分析显示PD与MDD有5个共同的GO_BP富集条目,分别是:GO:0007611(学习与记忆)、GO:0050890(认知)、GO:0007612(学习)、GO:0051384(对糖皮质激素的反应)、GO:0008306(联想学习)条目,提示PD和MDD均存在认知、学习、记忆及糖皮质激素反应通路功能障碍(P<0.05);PPI网络作图及关键基因分析提示NPTX2、PCSK1、DUSP6、SST、PPP1CB基因可能是PD和MDD共同的关键基因,在PD和MDD表达均显著降低(P<0.05)。结论:前额叶BA9区域认知通路功能障碍及NPTX2等基因表达减少可能是PD和MDD共同的分子病理。

Objective:To provide common clues for the research on the mechanism between Parkinson Disease(PD)and major depression disease(MDD)by analyzing the common differential genes(DEGs),the common pathways and hub genes between PD and MDD in the Brodman9(BA9)region of brain.Methods:GSE20168,GSE54567,GSE54568 and GSE54570 microarray data were downloaded from GEO database,and bioinformatics analysis packages such as limma,clusterProfiler and ggplot2 were called using R language to analyze PD and MDD co-expression with P<0.05 and logFC absolute value≥0.3 as criteria.Differential genes were further analyzed by GO and KEGG enrichment for common pathways,and protein-protein interaction(PPI)networks and key genes were identified using String database and cytoscape software.Results:There were 34 common DEGs in the BA9 region of PD and MDD patients,and 21 were up-regulated:SLC35E1,ATP8B1,TSR1,ZNF721,RIOK3,FBXW12,ZNF160,POLR1B,CACNA1I,MZT2B,PGF,RP11-403P17.4,RPL23AP32,DBT,PRR11,USP34,LRRFIP1,DSERG1,DIP2A,AEBP1 and DNAJB2,13 genes were down-regulated,namely NPTX2,PCSK1,SST,PPP1CB,SEC22B,ENPP4,NME5,CAPZA2,GLRB,ITFG1,GLIPR1,TM6SF1 and DUSP6.The functional enrichment analysis of DEGs showed that there were 5 common GO_BP terms between PD and MDD,namely:GO:0007611(learning or memory),GO:0050890(cognition),GO:0007612(learning),GO:0051384(response to glucocorticoids),GO:0008306(associative learning),suggesting that both PD and MDD have cognitive,learning,memory and glucocorticoid response pathway dysfunctions(P<0.05).PPI network mapping and hub genes analysis indicated that NPTX2,PCSK1,DUSP6,SST,and PPP1CB genes may be the common hub genes among PD and MDD,and their levels were significantly decreased in both PD and MDD(P<0.05).Conclusion:Cognitive pathway dysfunction and decreased expression of genes such as NPTX2 in BA9 region may be the common molecular pathology between PD and MDD.