FRI139 Identification Of Robust Aldosterone-Producing Adenomas-related Genes Using Adrenal Genome-wide Transcriptome Analysis

Abstract

Abstract Disclosure: S. Lee: None. T. Lee: None. G. Yoo: None. J. Lim: None. Primary aldosteronism (PA), the most common cause of secondary hypertension, is caused by aldosterone overproduction in one or two adrenal glands. It carries a higher risk of cardiovascular disease and mortality compared to essential hypertension. In an effort to identify the underlying molecular mechanisms regarding aldosterone secretion and cell proliferation in aldosterone-producing adenomas (APA), genome-wide transcriptome analyses have been conducted; however, there are still some limitations that need to be addressed since a relatively small number of samples were analyzed at a single center in most studies. In this study, we performed integrative and systematic analysis using adrenal transcriptome datasets to verify candidate genes robustly associated with APA and obtain more generalized signatures involved in the pathophysiology of PA. Three mRNA datasets for adrenal tissues (GSE8514, GSE60042, and GSE64957) were obtained from the Gene Expression Omnibus Database. For the first two datasets, normal adrenal samples from patients with renal cell carcinoma and adrenal tissue samples adjacent to APA were included as controls, respectively. In GSE64957, zona glomerulosa (ZG) and zona fasciculata (ZF) samples were analyzed separately in the current study (GSE64957ZG and GSE64957ZF). Differentially expressed gene (DEG) investigation and comparative analysis were conducted using the limma method. The selection criteria for APA-related genes were as follows: those that are significantly dysregulated in more than three of the four datasets and show a consistent trend of up- or down-regulation in four datasets. 5,375 genes were present in all transcriptome datasets; for the GSE64957ZG, 57 DEGs were identified in the APA group, among which 14, 7, and 37 genes were also dysregulated in the APA group of GSE64957ZF, GSE8514, and GSE60042, respectively. All comparisons among four lists of DEGs exhibited significant enrichment results. The highest degree of overlap was shown in the DEG pair of GSE64957ZG-GSE60042. As a result, approximately 20 genes (12 upregulated and 12 downregulated DEGs), including CYP11B2, PCP4, and ATP2A3, were selected as the final APA-related genes. This study demonstrated several candidate genes that are strongly relevant to APA by examining whole genome disease-related signatures. Besides CYP11B2, it seems that alteration in PCP4 and ATP2A3 genes would be much more involved in the pathogenesis of PA, which warrants further investigation along with validation for the role of the remaining genes. Presentation: Friday, June 16, 2023