Development and Validation of Hub Genes for Adrenal Aldosterone-Producing Adenoma by Integrated Bioinformatics Analysis

Hai Cai,1,* Shao-Ming Chen,2,* Zhi-Bin Ke,1,* Hang Chen,1,* Jun-Ming Zhu,1 Ting-Ting Lin,1 Fei Huang,3,4 Yong Wei,1 Qing-Shui Zheng,1 Xue-Yi Xue,1 Xiong-Lin Sun,1 Ning Xu1,3 1Department of Urology, Urology Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 2Department of Nuclear Medicine, First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 3Fujian Key Laboratory of Precision Medicine for Cancer, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, People’s Republic of China; 4Central Lab, The First Affiliated Hospital of Fujian Medical University, Fuzhou, 350005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ning Xu; Xiong-Lin Sun Tel +86-059187981687Email drxun@fjmu.edu.cn; sunxionglin@fjmu.edu.cnObjective: To develop and validate hub genes involving in the development and progression of primary aldosteronism (PA) and adrenal aldosterone-producing adenoma (APA).Materials and Methods: A total of four datasets of gene expression profiles related to APA were downloaded from GEO datasets. GSE60042 and GSE8514 were used to identify DEGs. Weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) network module analysis were conducted. GO and KEGG enrichment analysis was performed. GSE10927 and GSE33371 were used for further external validation.Results: We identified a total of 892 DEGs from GSE60042 and 1167 DEGs from GSE8514. WGCNA analysis demonstrated that the blue module (255 genes) and turquoise module (303 genes) were significantly correlated with APA. PPI networks were then constructed. GO term enrichment analysis suggested that cellular divalent inorganic cation homeostasis, calcium ion homeostasis, collagen-containing extracellular matrix, transport vesicle and metal ion transmembrane transporter activity were the vital annotations. KEGG pathway analysis found that these genes were significantly enriched in neuroactive ligand−receptor interaction, calcium signaling pathway. Finally, we identified a total of 11 candidate genes involving in the development and progression of APA and PA. Besides, two independent datasets (GSE10927 and GSE33371) were used for external validation, and there were seven hub genes successfully verified, including C3, GRM3, AVPR1A, WFS1, PTGFR, NTSR2, and JUN.Conclusion: These newly identified genes could contribute to the understanding of potential mechanism in APA and PA and might be promising targets for the treatment of APA and PA.Keywords: aldosterone-producing adenoma, bioinformatics, primary aldosteronism, gene expression omnibus datasets