Based ON Bioinformatics Analysis To Explore Candidate Genes Negatively Associated With Alzheimer's Disease And Colorectal Cancer

Objective:To explore the possible common differential genes(DEGs)that are negatively correlated with AD and colorectal cancer by bioinformatics analysis,and providing some theoretical basis for new prevention and treatment strategies for AD and colorectal cancer.Methods:(1)The gene microarray data GSE18309 and GSE164191 were downloaded from the Gene Expression Omnibus(GEO)Database.The online analysis tool GEO2R of GEO database was used to process the original data.Volcano plot was plotted by http://www.bioinformatics.com.cn,an online platform for data analysis and visualization.Heatmap was plotted by TCGAbiolinks,an online platform for data analysis and visualization.(2)According to the screening criteria of differential genes with |LogFC|>0.585,two Venn diagrams was respectively used to identify the intersecting parts of down-regulated DEGs in the AD group with up-regulated DEGs in the colorectal cancer group,and of up-regulated DEGs in the AD group with down-regulated DEGs in the colorectal cancer group.(3)Gene Ontology(GO)and Kyoto Gene and Genomic Encyclopedia(KEGG)were used to analyze the signalling pathway enrichment analysis of the screened common DEGs on TCGAbiolinks.(4)At last,the STRING database and Cytoscape software were then used to construct protein interaction networks(PPI)for the common DEGs,and the plugin MCODE in Cytoscape was applied to calculate the significant modules and the key genes(Hub)were selected based on the PPI network.Results:(1)There were 178 intersection DEGs between down-regulated AD group and up-regulated colorectal cancer group,and 31 intersection DEGs between up-regulated AD group and down-regulated colorectal cancer group.(2)The GO analysis of the common DEGs that were down-regulated in the AD group with up-regulated in the colorectal cancer group were mainly involved in Wnt receptor signaling pathway,cell growth regulation,and y-aminobutyric acid(GABA)receptor signaling pathway.KEGG pathway enrichment analysis of that was mainly enriched in Wnt signaling pathway,GABA receptor signaling,and regulation of epithelial-mesenchymal transition pathway.(3)The GO analysis of common DEGs up-regulated in AD group with down-regulated in colorectal cancer group were mainly involved in integrin-mediated signaling pathway and cell adhesion,KEGG signaling pathway enrichment analysis of that was mainly enriched in actin formation pathway,integrin signaling,and signaling by Rho family GTPases,and so on.(4)According to the MCODE method,the Hub genes of down-regulated in AD group with up-regulated in colorectal cancer group were WNT5A,FN1,GABRG1,GABRA2,GABRB3,NRXN1,KMT2D,WNT10A,LAMA4 and LAMA3,while the number of Hub genes in up-regulated in the AD group with down-regulated in the colorectal cancer group were only 7,such as WASL,PIK3C2A,GART,CMPK1,ITGB1,AP1S3 and ROCK1.Conclusion:Further screening and analysis of literature data on the above 17 key genes indicated that,WNT5A,WNT10A,GABRG1,GABRA2,GABRB3,FN1,NRXN1,and WASL may be key genes that are potentially linked to the blood gene expression profile of AD negatively associated with colorectal cancer,and as these genes are regulated in different directions in AD and colorectal cancer,leading to different disease outcomes,functional studies of these genes may provide new ideas for the prevention and treatment of AD and colorectal cancer.