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

In Silico Analysis of the Gene Expression Patterns between Aldosterone-Producing Adenoma and Nonfunctional Adrenocortical Adenoma.
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DOI:
10.1155/2021/9553637
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发表时间:
2021
期刊:
影响因子:
1.5
通讯作者:
Li J
Li J
中科院分区:
生物学4区
文献类型:
--
作者:
Dai Y;Li J;Wen H;Liu J;Li J

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原发性醛固酮增多症是继发性高血压最常见的形式,醛固酮瘤占原发性醛固酮增多症病例的很大比例。醛固酮瘤又称醛固酮腺瘤(aldosterone-producing adenoma,阿帕)。虽然关于阿帕的研究已经很多,但该病的发病机制尚未完全清楚。本研究旨在通过加权基因共表达网络(WGCNA)和差异表达基因(DEG)分析,找出阿帕和非功能性肾上腺皮质腺瘤(NFAA)基因表达模式的差异,只有符合两种方法相应标准的基因才被定义为真实的枢纽基因,然后用于进一步分析。发现了29个真实的hub基因,其中大部分基因在磷脂代谢过程中富集。WISP 2、S100 A10、SSTR 5-AS 1、SLC 29 A1、APOC 1和SLITRK 4是6个真实的中枢基因,在合并数据集和验证数据集之间具有相同的基因表达模式,其中3个基因间接或直接参与脂质代谢,包括WISP 2、S100 A10和APOC 1。根据DEGs的基因表达模式,我们推测了5种对阿帕有潜在治疗价值的候选药物,其中之一是磷脂生物合成抑制剂放线菌酮。磷脂代谢可能是阿帕的重要病理生理机制。我们的研究为阿帕的病理生理机制提供了新的视角,并提供了一些可能成为抗阿帕有效药物的小分子物质。
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.
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