Abstract

Primary aldosteronism is the most common form of secondary hypertension, and aldosteronoma makes up a significant proportion of primary aldosteronism cases. Aldosteronoma is also called aldosterone-producing adenoma (APA). Although there have been many studies about APA, the pathogenesis of this disease is not yet fully understood. In this study, we aimed to find out the difference of gene expression patterns between APA and nonfunctional adrenocortical adenoma (NFAA) using a weighted gene coexpression network (WGCNA) and differentially expressed gene (DEG) analysis; only the genes that meet the corresponding standards of both methods were defined as real hub genes and then used for further analysis. Twenty-nine real hub genes were found out, most of which were enriched in the phospholipid metabolic process. WISP2, S100A10, SSTR5-AS1, SLC29A1, APOC1, and SLITRK4 are six real hub genes with the same gene expression pattern between the combined and validation datasets, three of which indirectly or directly participate in lipid metabolism including WISP2, S100A10, and APOC1. According to the gene expression pattern of DEGs, we speculated five candidate drugs with potential therapeutic value for APA, one of which is cycloheximide, an inhibitor for phospholipid biosynthesis. All the evidence suggests that phospholipid metabolism may be an important pathophysiological mechanism for APA. Our study provides a new perspective regarding the pathophysiological mechanism of APA and offers some small molecules that may possibly be effective drugs against APA.

Highlights

  • Primary aldosteronism (PA) is widely recognized as the common causative agent of hypertension cases, especially for treatment-resistant hypertension [1]

  • A nationwide multicenter study in Japan revealed that 50.8% of total adrenal incidentalomas were nonfunctional adrenocortical adenoma (NFAA), while only 5.1% were aldosterone-producing adenoma (APA) [5]. is study aimed to find out the differences of the gene expression pattern between these kinds of states which may let us further understand the pathogenesis of APA

  • For Gene Ontology (GO) enrichment analysis, 39 gene sets were enriched in the APA phenotype with P values

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Summary

Introduction

Primary aldosteronism (PA) is widely recognized as the common causative agent of hypertension cases, especially for treatment-resistant hypertension [1]. PA is mainly caused by aldosterone-producing adenoma (APA) [4], an adrenal tumor that excessively secretes aldosterone, which leads to hypertension and hyperkalemia. A nationwide multicenter study in Japan revealed that 50.8% of total adrenal incidentalomas were NFAA, while only 5.1% were APA [5]. Is study aimed to find out the differences of the gene expression pattern between these kinds of states which may let us further understand the pathogenesis of APA. Previous studies have identified somatic mutations in the potassium channel gene KCNJ5 and the calcium channel gene CACNA1D, which contribute to aldosterone production and cell proliferation in adrenal glomerulosa [6, 7].

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