Screening Of The Key Genes And Signaling Pathways For Diabetic Nephropathy Based On The GEO Database

ObjectiveIn this study,the key genes and signaling pathways of diabetic nephropathy(DN)and its underlying roles were explored by bioinformatics methods.MethodsFour datasets GSE30528,GSE47183,GSE104948 and GSE96804 were downloaded from Gene Expression Omnibus(GEO)database.The differentially expressed genes(DEGs)were identified by "limma" package from three datasets(GSE30528,GSE47183 and GSE104948).Using the "RobustRankAggreg"package to screen the overlapping DEGs.Then,the protein-protein interactions(PPIs)of the overlapping DEGs were analyzed by the search tool for the retrieval of interacting genes/proteins(STRING)database.The top 15 hub genes were screened by using 10 randomly selected algorithms in CytoHubba,respectively,and then the"UpSetR" package was used to screen the common hub genes of the 10 algorithms.Through logistic regression analysis further screen the hub genes.GSE96804 gene expression data were used to verify the expression level of hub gene.The diagnostic effectiveness of hub gene was predicted by Receiver Operator Characteristic Curve(ROC)analysis.Correlation analysis and Enrichment analysis for individual hub genes was implemented to make further identification of underlying functions of the interesting hub gene involved in DN.ResultsIn total,55 DEGs,including 38 upregulated and 17 downregulated genes,were identified from the three datasets.Four hub genes(FN1,CD44,C1QB,C1QA)were screened by R package "UpSetR".And FN1 was an important core gene of DN.Correlation analysis and enrichment analysis showed that FN1 was positively correlated with THBS2,COL1A2,COL6A3,and CD44,acting on the ECM-receptor interaction pathway to mediate the development of diabetic nephropathy.ConclusionsIn summary,we investigated the potential biomarkers for DN using integrated bioinformatic analysis.We identified four candidate genes:FN1,C1QA,C1QB,and CD44.On further investigating the biological functions of FN1,we found that FN1 was positively correlated with THBS2,COL1A2,COL6A3,and CD44,and commonly involved in the development of diabetic nephropathy through the ECM receptor interaction pathway.