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醛固酮腺瘤与无功能性肾上腺皮质腺瘤基因表达谱的计算机分析。

In Silico Analysis of the Gene Expression Patterns between Aldosterone-Producing Adenoma and Nonfunctional Adrenocortical Adenoma.

机构信息

Department of Cardiovascular Medicine, The First Nanning People's Hospital, Nanning, Guangxi 530016, China.

Department of Nuclear Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530031, China.

出版信息

Genet Res (Camb). 2021 Oct 4;2021:9553637. doi: 10.1155/2021/9553637. eCollection 2021.

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. , , , , , and 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 , , and . 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.

摘要

原发性醛固酮增多症是继发性高血压最常见的形式,醛固酮瘤构成了原发性醛固酮增多症病例的重要比例。醛固酮瘤也称为产生醛固酮的腺瘤(APA)。尽管已经有许多关于 APA 的研究,但该疾病的发病机制仍未完全阐明。在这项研究中,我们使用加权基因共表达网络分析(WGCNA)和差异表达基因分析(DEG),旨在找出 APA 和无功能肾上腺皮质腺瘤(NFAA)之间基因表达模式的差异;只有同时满足这两种方法相应标准的基因才被定义为真正的枢纽基因,然后用于进一步分析。发现了 29 个真正的枢纽基因,其中大多数富集在磷脂代谢过程中。、、、、、和是六个在联合和验证数据集之间具有相同基因表达模式的真正枢纽基因,其中三个间接或直接参与脂质代谢,包括、和。根据 DEG 的基因表达模式,我们推测了五种对 APA 具有潜在治疗价值的候选药物,其中一种是环己酰亚胺,一种磷脂生物合成抑制剂。所有证据表明,磷脂代谢可能是 APA 的一个重要病理生理机制。我们的研究为 APA 的病理生理机制提供了新的视角,并提供了一些可能对 APA 有效的小分子药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a10/8505127/789335f10cb0/GR2021-9553637.001.jpg

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