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血清微小RNA作为原发性醛固酮增多症的外周标志物。

Serum microRNAs as peripheral markers of primary aldosteronism.

作者信息

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

机构信息

Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.

Department of Surgery, Karlstad Central Hospital, Karlstad, Sweden.

出版信息

Front Endocrinol (Lausanne). 2025 Mar 20;16:1511096. doi: 10.3389/fendo.2025.1511096. eCollection 2025.

Abstract

BACKGROUND

Primary aldosteronism (PA) is the principal cause of secondary hypertension; it leads to significantly elevated cardiovascular morbidity and mortality, but only a fraction of its cases ever get detected, partially due to diagnostic procedures that are difficult to perform and to interpret. More straightforward diagnostic methods are needed. Lateralized, or unilateral PA (uPA), is best treated by surgery. Bilateral PA (bPA) is treated medically.

AIM

The aim of our study was to explore microRNA (miRNA) in peripheral blood as markers of PA, uPA and bPA.

METHODS

In groups of subjects with primary hypertension (HT, n = 11), bPA (n = 12), and uPA (n = 16), peripheral serum was used for isolation of total RNA, library preparation, and NGS sequencing to achieve a comparative analysis of miRNA expression. Five-fold cross-validation support vector machine learning (ML) models were employed to search for miRNA that could be used as markers of PA and its forms.

RESULTS

In our cohort of patients, the discovered combinations of miRNAs could, with a high level of accuracy, sensitivity, and specificity, characterize the difference between HT and PA, as well as between a combined group of HT + bPA vs. uPA. The differentiating parameters were moderately good for comparison of bPA vs. uPA.

CONCLUSION

Within our patient cohort, and using ML, the study identified distinctly different miRNA profiles between HT and PA, as well as between bPA and uPA. Further validation studies may lead to the emergence of a new tool for clinical diagnostics of PA.

摘要

背景

原发性醛固酮增多症(PA)是继发性高血压的主要病因;它会导致心血管发病率和死亡率显著升高,但只有一小部分病例能被检测出来,部分原因是诊断程序操作和解读困难。因此需要更直接的诊断方法。单侧原发性醛固酮增多症(uPA)最好通过手术治疗。双侧原发性醛固酮增多症(bPA)则采用药物治疗。

目的

本研究旨在探索外周血中的微小RNA(miRNA)作为PA、uPA和bPA的标志物。

方法

在原发性高血压(HT,n = 11)、bPA(n = 12)和uPA(n = 16)的受试者组中,使用外周血清分离总RNA、制备文库并进行NGS测序,以实现miRNA表达的比较分析。采用五重交叉验证支持向量机学习(ML)模型来寻找可作为PA及其类型标志物的miRNA。

结果

在我们的患者队列中,发现的miRNA组合能够以较高的准确性、敏感性和特异性来表征HT与PA之间以及HT + bPA联合组与uPA之间的差异。区分参数在比较bPA与uPA时表现中等。

结论

在我们的患者队列中,并使用ML,该研究确定了HT与PA之间以及bPA与uPA之间明显不同的miRNA谱。进一步的验证研究可能会产生一种用于PA临床诊断的新工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7744/11967191/11cd1f5a9cc2/fendo-16-1511096-g001.jpg

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