Targeted Multiplex Proteomics for the Development and Validation of Biomarkers in Primary Aldosteronism Subtyping.

IF 5.3 1区医学 Q1 ENDOCRINOLOGY & METABOLISM European Journal of Endocrinology Pub Date : 2024-11-18 DOI:10.1093/ejendo/lvae148

Fangli Zhou, Yun Ding, Tao Chen, Qiming Tang, Jingjing Zhang, Sheeno Thyparambil, Bo Jin, Zhi Han, C James Chou, James Schilling, Ruben Y Luo, Haoming Tian, Karl G Sylvester, John C Whitin, Harvey J Cohen, Doff B McElhinney, Li Tian, Xuefeng B Ling, Yan Ren

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Abstract

Objective: Primary aldosteronism (PA), a significant cause of secondary hypertension affecting approximately 10% of patients with severe hypertension, exacerbates cardiovascular and cerebrovascular complications even after blood pressure control. PA is categorized into two main subtypes: unilateral aldosterone-producing adenomas (APA) and bilateral hyperaldosteronism (BHA), each requiring distinct treatment approaches. Accurate subtype classification is crucial for selecting the most effective treatment. The goal of this study was to develop novel blood-based proteomic biomarkers to differentiate between APA and BHA subtypes in patients with PA.

Design and methods: Five subtyping differential protein biomarker candidates (APOC3, CD56, CHGA, KRT5, and AZGP1) were identified through targeted proteomic profiling of plasma. The subtyping efficiency of these biomarkers was assessed at both the tissue gene expression and blood protein expression levels. To explore the underlying biology of APA and BHA, significant differential pathways were investigated.

Results: The five-protein panel proved highly effective in distinguishing APA from BHA in both tissue and blood samples. By integrating these five protein biomarkers with aldosterone and renin, our blood-based predictive methods achieved remarkable ROC AUCs of 0.986 (95% CI: 0.963-1.000) for differentiating essential hypertension (EH) from PA, and 0.922 (95% CI: 0.846-0.998) for subtyping APA versus BHA. These outcomes surpass the performance of the existing Kobayashi score subtyping system. Furthermore, the study validated differential pathways associated with the pathophysiology of primary aldosteronism, aligning with current scientific knowledge and opening new avenues for advancing PA care.

Conclusions: The new blood-based biomarkers for PA subtyping hold the potential to significantly enhance clinical utility and advance the practice of PA care.

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靶向多重蛋白质组学用于开发和验证原发性醛固酮增多症亚型的生物标记物

目的：原发性醛固酮增多症（PA）是继发性高血压的重要病因，约占严重高血压患者的 10%，即使在控制血压后仍会加重心脑血管并发症。醛固酮增多症主要分为两种亚型：单侧醛固酮生成腺瘤（APA）和双侧醛固酮增多症（BHA），每种亚型都需要不同的治疗方法。准确的亚型分类对于选择最有效的治疗方法至关重要。本研究的目的是开发基于血液的新型蛋白质组生物标志物，以区分 PA 患者的 APA 和 BHA 亚型：通过对血浆进行靶向蛋白质组学分析，确定了五个亚型差异蛋白质生物标志物候选者（APOC3、CD56、CHGA、KRT5和AZGP1）。在组织基因表达和血液蛋白表达水平上评估了这些生物标志物的亚型效率。为了探索 APA 和 BHA 的潜在生物学特性，研究人员还对重要的差异途径进行了调查：结果：在组织和血液样本中，五种蛋白面板被证明能非常有效地区分 APA 和 BHA。通过将这五种蛋白生物标记物与醛固酮和肾素整合，我们基于血液的预测方法在区分本质性高血压（EH）与PA方面取得了0.986（95% CI：0.963-1.000）的显著ROC AUC，在APA与BHA的亚型划分方面取得了0.922（95% CI：0.846-0.998）的显著ROC AUC。这些结果超过了现有的小林评分亚型系统。此外，该研究还验证了与原发性醛固酮增多症病理生理学相关的不同途径，与当前的科学知识保持一致，并为推进PA治疗开辟了新途径：结论：用于 PA 亚型鉴定的新型血液生物标记物有望显著提高临床实用性，推动 PA 护理实践的发展。

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

European Journal of Endocrinology 医学-内分泌学与代谢

CiteScore

9.80

自引率

3.40%

发文量

354

审稿时长

1 months

期刊介绍： European Journal of Endocrinology is the official journal of the European Society of Endocrinology. Its predecessor journal is Acta Endocrinologica. The journal publishes high-quality original clinical and translational research papers and reviews in paediatric and adult endocrinology, as well as clinical practice guidelines, position statements and debates. Case reports will only be considered if they represent exceptional insights or advances in clinical endocrinology. Topics covered include, but are not limited to, Adrenal and Steroid, Bone and Mineral Metabolism, Hormones and Cancer, Pituitary and Hypothalamus, Thyroid and Reproduction. In the field of Diabetes, Obesity and Metabolism we welcome manuscripts addressing endocrine mechanisms of disease and its complications, management of obesity/diabetes in the context of other endocrine conditions, or aspects of complex disease management. Reports may encompass natural history studies, mechanistic studies, or clinical trials. Equal consideration is given to all manuscripts in English from any country.