Gao Yinjie, Ma Xiaosen, Wang Huiping, Cui Yunying, Zhang Yushi, Nie Min, Tong Anli
NHC Key Laboratory of Endocrinology (Peking Union Medical College Hospital), Department of Endocrinology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Department of Urology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100730, China.
Int J Endocrinol. 2021 Oct 12;2021:4926323. doi: 10.1155/2021/4926323. eCollection 2021.
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.
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.
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 ( = 2.00X10). In the KEGG pathway analysis, calcium signaling pathway ( = 4.38X10) and the aldosterone synthesis and secretion ( = 8.73X10) 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, < 0.001; 3.753 folds of NFA, = 0.002; and 11.487 folds of NFA, = 0.018).
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.
既往研究已对醛固酮分泌性腺瘤（APA）醛固酮过度分泌的转录调控进行了调查。我们旨在通过生物信息学分析和对表达谱的实验验证，系统地研究与APA潜在分子机制相关的基因和通路。
本研究基于三个基因表达谱（GSE64957、GSE8514和GSE60042）进行。通过生物信息学分析进行差异表达基因（DEG）研究、功能和通路富集分析以及蛋白质-蛋白质相互作用（PPI）网络分析。为了通过定量PCR进行验证，我们的队列纳入了11例无功能肾上腺腺瘤（NFA）患者和13例APA患者的组织。
在本研究中，进行了生物信息学分析，鉴定出182个上调的DEG和88个下调的DEG。正如预期的那样，上调的DEG主要参与钙离子稳态（=2.00X10）。在KEGG通路分析中，钙信号通路（=4.38X10）和醛固酮合成与分泌（=8.73X10）得到富集。此外，进行定量PCR以检测DEG交集处7个上调基因（PCP4、ATP2A3、CYP11B2、CLCN5、HTR4、VDR和AQP2）的表达。与NFA相比，APA样本中CYP11B2、HTR4和AQP2的mRNA水平显著升高（分别为NFA的24.420倍，<0.001；NFA的3.753倍，=0.002；以及NFA的11.487倍，=0.018）。
总之，本研究从生物信息学分析和我们的队列中显示了几个高表达的候选基因。此外，正如预期的那样，DEG在醛固酮合成与分泌以及钙信号通路中得到富集。
