Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
The Center for Personalized Medicine for Healthy Aging, Tokyo Medical and Dental University, Tokyo, Japan.
Front Endocrinol (Lausanne). 2022 Dec 13;13:1073328. doi: 10.3389/fendo.2022.1073328. eCollection 2022.
Primary bilateral macronodular adrenal hyperplasia (PBMAH), a rare cause of Cushing syndrome, is often diagnosed as a bilateral adrenal incidentaloma with subclinical cortisol production. Circulating microRNAs (miRNAs) are a characteristic of adrenocortical adenomas, but miRNA expression in PBMAH has not been investigated. We aimed to evaluate the circulating miRNA expression in patients with PBMAH and compare them with those in patients with non-functioning adrenocortical adenoma (NFA) and cortisol-producing adrenocortical adenoma (CPA).
miRNA profiling of plasma samples from four, five, and five patients with NFA, CPA, and PBMAH, respectively, was performed. Selected miRNA expressions were validated using quantitative RT-PCR.
PBMAH samples showed distinct miRNA expression signatures on hierarchical clustering while NFA and CPA samples were separately clustered. PBMAH was distinguished from the adenoma group of NFA and CPA by 135 differentially expressed miRNAs. Hsa-miR-1180-3p, hsa-miR-4732-5p, and hsa-let-7b-5p were differentially expressed between PBMAH and adenoma ( = 0.019, 0.006, and 0.003, respectively). Furthermore, PBMAH could be classified into two subtypes based on miRNA profiling: subtype 1 with a similar profile to those of adenoma and subtype 2 with a distinct profile. Hsa-miR-631, hsa-miR-513b-5p, hsa-miR-6805-5p, and hsa-miR-548av-5p/548k were differentially expressed between PBMAH subtype 2 and adenoma ( = 0.027, 0.027, 0.027, and 1.53E-04, respectively), but not between PBMAH, as a whole, and adenoma.
Circulating miRNA signature was identified specific for PBMAH. The existence of subtype-based miRNA profiles may be associated with the pathophysiological heterogeneity of PBMAH.
原发性双侧结节性肾上腺增生症（PBMAH）是库欣综合征的一种罕见病因，常被诊断为双侧肾上腺意外瘤伴亚临床皮质醇生成。循环 microRNAs（miRNAs）是肾上腺皮质腺瘤的特征，但 PBMAH 中的 miRNA 表达尚未被研究。我们旨在评估 PBMAH 患者的循环 miRNA 表达，并将其与无功能肾上腺皮质腺瘤（NFA）和分泌皮质醇的肾上腺皮质腺瘤（CPA）患者进行比较。
对 4 例、5 例和 5 例 NFA、CPA 和 PBMAH 患者的血浆样本进行 miRNA 谱分析。使用定量 RT-PCR 验证选定的 miRNA 表达。
PBMAH 样本在层次聚类中表现出明显的 miRNA 表达特征，而 NFA 和 CPA 样本则分别聚类。PBMAH 与 NFA 和 CPA 的腺瘤组通过 135 个差异表达 miRNA 区分。hsa-miR-1180-3p、hsa-miR-4732-5p 和 hsa-let-7b-5p 在 PBMAH 与腺瘤之间表达差异（ = 0.019、0.006 和 0.003）。此外，根据 miRNA 谱分析，PBMAH 可分为两种亚型：与腺瘤相似的亚型 1 和具有独特特征的亚型 2。hsa-miR-631、hsa-miR-513b-5p、hsa-miR-6805-5p 和 hsa-miR-548av-5p/548k 在 PBMAH 亚型 2 与腺瘤之间表达差异（ = 0.027、0.027、0.027 和 1.53E-04），但 PBMAH 作为一个整体与腺瘤之间无差异。
鉴定出了 PBMAH 特异性的循环 miRNA 特征。基于 miRNA 图谱的亚型存在可能与 PBMAH 的病理生理异质性有关。
