阿尔茨海默病自噬相关基因的筛选及其通路分析OACSTPCD

Objective Screen autophagy related genes of Alzheimer disease(AD)based on microarray analysis,conduct pathway analysis and identify key genes in order to explore potential pathogenesis and therapeutic targets.Methods The GSE33000 dataset was downloaded from GEO Database,and the differentially expressed genes of AD were obtained by R software limma package.Autophagy-related genes were downloaded from Human Autophagy Database,Human Autophagy Modulator Database and GeneCard Database,respectively,and the autophagy-related gene set was obtained.The AD autophagy-related genes were obtained through intersecting the differentially expressed genes with the autophagy-related gene set.The R software packages such as org.Hs.eg.db and clusterProfiler were used to perform gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,the online software Search Tool for the Retrieval of Interacting Genes(STRING)was used to conduct protein-protein interaction network analysis,and the key genes were predicted based on MCC algorithm.Results A total of 66 autophagy related genes were obtained,of which 41 genes were up-regulated and 25 genes were down-regulated.Gene enrichment analysis showed that cellular components in GO analysis were mainly enriched in phagocytic vesicle membrane,secretory granule membrane,membrane microdomain,late endosome,etc.,and molecular functions were mainly enriched in Toll-like receptor binding,ubiquitin-like protein ligase binding,etc.,and biological processes were enriched in regulation of autophagy,positive regulation of cellular catabolic process,response to lipopolysaccharide,regulation of inflammatory response,cellular response to external stimulus,etc.In KEGG enrichment analysis,the differentially expressed autophagy-related genes were mainly concentrated in NOD-like receptor signaling pathway,lipid and atherosclerosis,forkhead box protein O(FoxO)signaling pathway,etc.Our research completed the construction of protein-protein interaction(PPI),identified 10 key genes,and screened out that interleukin-6(IL-6)and signal transducer and activator of transcription 3(STAT3)were closely related to AD.Conclusions Ten key autophagy-related genes were obtained in this study,among which IL-6 and STAT3 are more closely related to AD.