Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
Endocrinol Metab (Seoul). 2024 Apr;39(2):375-386. doi: 10.3803/EnM.2023.1827. Epub 2024 Mar 21.
Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.
We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis.
The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations.
Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.
甲状旁腺腺瘤(PA)是一种常见的内分泌疾病,与多种并发症相关,但疾病的病理生理学仍不完全清楚。本研究旨在通过定量蛋白质组学分析,根据功能和体积鉴定 PA 的关键调控蛋白和途径。
我们对来自韩国三家医院的 15 例福尔马林固定、石蜡包埋的 PA 样本进行了回顾性研究。提取蛋白质,消化后,使用液相色谱-串联质谱分析得到的肽段。采用 Pearson 相关分析鉴定与临床变量显著相关的蛋白质。使用 Ingenuity 通路分析(IPA)分析经典通路和转录因子。
参与者的中位年龄为 52 岁,60.0%为女性。在分析的 8153 个蛋白质组中,有 496 个与腺瘤体积呈显著正相关,而 431 个与甲状旁腺激素(PTH)水平显著相关。SLC12A9、LGALS3 和 CARM1 与腺瘤体积呈正相关,而 HSP90AB2P、HLA-DRA 和 SCD5 则呈负相关。DCPS、IRF2BPL 和 FAM98A 是与 PTH 水平呈正相关的主要蛋白质,而 SLITRK4、LAP3 和 AP4E1 则呈负相关。经典通路分析表明,RAN 和组蛋白去乙酰化酶信号通路与 PTH 水平和腺瘤体积均呈正相关,而上皮细胞黏附连接途径则呈负相关。
本研究鉴定了与 PA 相关的关键蛋白和途径,为潜在的治疗靶点提供了依据。这些发现强调了蛋白质组学在理解疾病病理生理学中的重要性,需要进一步研究。