Developing the novel diagnostic model and potential drugs by integrating bioinformatics and machine learning for aldosterone-producing adenomas

Abstract

Background: Aldosterone-producing adenomas (APA) are a common cause of primary aldosteronism (PA), a clinical syndrome characterized by hypertension and electrolyte disturbances. If untreated, it may lead to serious cardiovascular complications. Therefore, there is an urgent need for potential biomarkers and targeted drugs for the diagnosis and treatment of aldosteronism.Methods: We downloaded two datasets (GSE156931 and GSE60042) from the GEO database and merged them by de-batch effect, then screened the top50 of differential genes using PPI and enriched them, followed by screening the Aldosterone adenoma-related genes (ARGs) in the top50 using three machine learning algorithms. We performed GSEA analysis on the ARGs separately and constructed artificial neural networks based on the ARGs. Finally, the Enrich platform was utilized to identify drugs with potential therapeutic effects on APA by tARGseting the ARGs.Results: We identified 190 differential genes by differential analysis, and then identified the top50 genes by PPI, and the enrichment analysis showed that they were mainly enriched in amino acid metabolic pathways. Then three machine learning algorithms identified five ARGs, namely, SST, RAB3C, PPY, CYP3A4, CDH10, and the ANN constructed on the basis of these five ARGs had better diagnostic effect on APA, in which the AUC of the training set is 1 and the AUC of the validation set is 0.755. And then the Enrich platform identified drugs tARGseting the ARGs with potential therapeutic effects on APA.Conclusion: We identified five ARGs for APA through bioinformatic analysis and constructed Artificial neural network (ANN) based on them with better diagnostic effects, and identified drugs with potential therapeutic effects on APA by tARGseting these ARGs. Our study provides more options for the diagnosis and treatment of APA.