Objective:To explore the key genes and its biological functions of aldosterone producing adenoma (APA) using bioinformatics analysis.Methods:Differentially expressed genes of APA were identified from two training datasets GSE60042 and GSE64957 in GEO database. Function and pathway enrichment analyses for differentially expressed genes were performed and transcriptional regulation network among these genes were determined. Hub genes were extracted by node analysis from the protein-protein interaction (PPI) network. The expression of key genes was verified by a testing dataset GSE8514. Receiver operating characteristic(ROC) curve analysis was applied to assess the diagnostic efficiency of key genes in APA. The biofunction of each key gene were determined by gene set enrichment analysis (GSEA).Results:A total of 68 differentially expressed genes, including 33 up-regulated genes and 35 down-regulated genes, were detected from the training datasets. These genes were mainly enriched in aldosterone biosynthetic process, calcium signaling pathway, serotonin receptor signaling pathway, transcriptional activator activity, and regulation of transcription. JUN and VDR were at the center of the transcriptional factor-gene network. Furthermore, we identified nine Hub genes from the PPI network. In testing dataset, CYP11B2 and VDR showed the higher expression, while JUN, NFKBIZ, EGR3, and KLF6 showed lower expression in APA (all P<0.05), and the value of area under ROC curve analysis was 0.936, 0.833, 0.953, 0.854, 0.868, and 0.929, respectively. GSEA indicated the alter of key genes in APA led to up-regulation of the steroid biosynthesis, cell adhesion molecules, immune cells signaling pathway, and complement and coagulation cascades [all normalized enrichment score (NES)>1.5, P<0.05], but down-regulation of the DNA replication, ribosome, and autophagy (all NES<-1.5, P<0.05). Conclusion:Results of bioinformatics indicate that JUN and VDR are key transcriptional factors, and CYP11B2, NFKBIZ, EGR3, and KLF6 are the key genes for APA, which are involved in the steroid biosynthesis, cell adhesion molecules, immune cells signaling pathway in APA.