Abstract
Purpose Previous studies have investigated the transcriptional modulations of aldosterone overproduction of aldosterone-producing adenomas (APAs). We aimed to systematically study the genes and pathways associated with molecular mechanism underlying APA by bioinformatics analysis and experimental validation for the expression profile. Methods This study was performed based on three gene expression profiles (GSE64957, GSE8514, and GSE60042). Differentially expressed gene (DEG) investigation, function and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed by the bioinformatics analysis. For the validation with quantitative PCR, tissues from 11 patients with nonfunctioning adrenal adenoma (NFA) and 13 with APA were included in our cohort. Results In this study, the bioinformatics analysis was performed and 182 upregulated and 88 downregulated DEGs were identified. As expected, the upregulated DEGs were primarily involved in calcium ion homeostasis (p = 2.00X10−4). In the KEGG pathway analysis, calcium signaling pathway (p = 4.38X10−6) and the aldosterone synthesis and secretion (p = 8.73X10−6) were enriched. Moreover, quantitative PCR was performed to detect the expression of 7 upregulated genes (PCP4, ATP2A3, CYP11B2, CLCN5, HTR4, VDR, and AQP2) among the intersection of DEGs. The mRNA levels of CYP11B2, HTR4, and AQP2 were significantly increased in APA samples compared to NFA (24.420 folds of NFA, p < 0.001; 3.753 folds of NFA, p = 0.002; and 11.487 folds of NFA, p = 0.018). Conclusion In summary, the present study showed several candidate genes with high expression from bioinformatics analysis and our cohort. Also, the DEGs were enriched in aldosterone synthesis and secretion and calcium signaling pathway as expected.
Highlights
Primary aldosteronism (PA) is the most common form of endocrine hypertension with a prevalence of 5–20% in patients with hypertension and is characterized by the excessive production of aldosterone [1, 2]
Differentially expressed gene (DEG) in aldosterone-producing adenoma (APA) Samples Compared with Control adrenal glands (AAG) Samples
A total of 182 upregulated and 88 downregulated DEGs were identified by GEO2R analysis. e intersection DEGs of the three datasets consisted of 6 genes, PCP4, ATP2A3, PPP4R4, CTNND2, CYP11B2, and CLRN1
Summary
Primary aldosteronism (PA) is the most common form of endocrine hypertension with a prevalence of 5–20% in patients with hypertension and is characterized by the excessive production of aldosterone [1, 2]. Several studies investigated the gene expression profile of APAs compared to normal adrenals or adjacent adrenal cortexes with the aim of identifying transcriptional modulations of aldosterone overproduction [4, 5]. Numerous genes, including the ones encoding steroidogenic enzymes such as CYP11B2, CYP11B1, CYP21A1, CYP11A1, CYP17A, and HSD3B2, few genes involved in calcium signaling or endoplasmic reticulum calcium storage such as CALM2, CALR, and CAMK-I, and several G-protein-coupled hormone receptors such as receptors of GnRH, LH, vasopressin, and serotonin, have been identified in previous studies as International Journal of Endocrinology differentially expressed in APAs and the adrenal cortexes [5, 8]. Bioinformatics analysis and experimental validation for the expression profile of APAs compared with controls were studied. Several DEGs from databases were verified in our cohort with 13 tissue samples from APA and 11 from nonfunctioning adrenal adenoma (NFA)
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