Searching for peripheral proteomic markers of primary aldosteronism.

IF 2.9 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Endocrine Pub Date : 2025-09-01 Epub Date: 2025-06-13 DOI:10.1007/s12020-025-04302-y

Nikita Makhnov, Fredrik Axling, Elham Barazeghi, Peter Stålberg, Tobias Åkerström, Per Hellman

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引用次数: 0

Abstract

Purpose: Primary aldosteronism (PA) is prevalent among hypertensive patients, and associated with worsened cardiovascular outcomes compared to essential hypertension (HT). Screening and diagnostics for PA are currently complicated and invasive, why new methods are needed. Unilateral PA (uPA) is best treated surgically, and bilateral PA (bPA) - medically. No validated proteomic diagnostic test has been found yet. Our aim was to explore proteomic markers in peripheral serum to discriminate between HT, PA, uPA and bPA.

Methods: Eighty-eight hypertensive individuals were evaluated for PA, and diagnosed with HT (n = 30); bPA (n = 29); and uPA (n = 29). Serum samples from these study groups were analyzed by Olink® Explore 384 Cardiometabolic Panel. A machine learning model based on ridge logistic regression with a stratified 5-fold cross-validation was used to identify HT, PA, bPA and uPA.

Results: In the study groups, 56 circulating proteins were significantly different, and some of them specifically: 4 between PA vs. HT; 3 between bPA vs. uPA; 1 between bPA vs. HT; 9 between uPA vs. HT; 1 between HT vs. bPA vs. uPA. Three proteins with strongest differentiation (Coagulation factor IX for PA vs. HT; dipeptidyl peptidase 4 for uPA vs. HT and bPA; heat shock protein B1 for bPA vs. uPA) were validated by enzyme-linked immunosorbent assay. Our machine learning model could successfully identify 95% of HT, bPA, and uPA samples.

Conclusion: Serum protein biomarkers may serve as a tool for discriminating HT, PA, uPA and bPA. Further studies are needed to support our results.

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寻找原发性醛固酮增多症的外周蛋白质组学标志物。

目的：原发性醛固酮增多症（PA）在高血压患者中普遍存在，与原发性高血压（HT）相比，其心血管预后恶化相关。目前PA的筛查和诊断是复杂和侵入性的，为什么需要新的方法。单侧PA （uPA）最好通过手术治疗，而双侧PA （bPA）最好通过医学治疗。目前尚未发现有效的蛋白质组学诊断方法。我们的目的是探索外周血清中的蛋白质组学标记物来区分HT、PA、uPA和bPA。方法：对88例高血压患者进行PA检查，并诊断为HT (n = 30)；bPA (n = 29)；和uPA （n = 29）。这些研究组的血清样本通过Olink®Explore 384心脏代谢小组进行分析。采用基于岭逻辑回归的机器学习模型和分层5重交叉验证来识别HT、PA、bPA和uPA。结果：在各研究组中，56种循环蛋白存在显著差异，其中一些具有特异性：PA与HT之间有4种；bPA与uPA的比值为3；bPA与HT的比值为1；uPA与HT的比值为9；在HT、bPA和uPA之间。三种分化最强的蛋白(凝血因子IX对PA和HT；二肽基肽酶4用于uPA对抗HT和bPA；热休克蛋白B1 （bPA vs. uPA）通过酶联免疫吸附试验验证。我们的机器学习模型可以成功识别95%的HT、bPA和uPA样品。结论：血清蛋白生物标志物可作为HT、PA、uPA和bPA的鉴别工具。需要进一步的研究来支持我们的结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Endocrine ENDOCRINOLOGY & METABOLISM-

CiteScore

6.50

自引率

5.40%

发文量

295

审稿时长

1.5 months

期刊介绍： Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology. Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted. Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.