Circulating microRNAs as Diagnostic Markers in Primary Aldosteronism

MacKenzie, Scott; Saunders, Hannah; Kralingen, Josie C van; Robertson, Stephen M.; Riddell, Alexandra; Zennaro, Maria‐Christina; Davies, Eleanor

doi:10.3390/cancers13215312

Cited by 7 publications

(3 citation statements)

References 51 publications

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“…Specific non-hormonal biomarkers could potentially help in situations where (i) hormone levels are not applicable-for instance, exogenous glucocorticoid administration; (ii) hormone dosages are not informative, due to situations interfering with hormone assays [28]; (iii) hormone dosages are borderline, not providing a proper classification of patients. Some non-hormonal markers of endocrine hypertension have been proposed, including specifically targeted metabolomics [29], and miRNAs [30,31]. Blood methylation marks may also be suitable for direct measurement of hormone excess on peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Whole blood methylome-derived features to discriminate endocrine hypertension

Armignacco

Reel

et al. 2022

Clin Epigenet

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Background Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. Results Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. Conclusions The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder.

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Section: Discussionmentioning

confidence: 99%

Whole blood methylome-derived features to discriminate endocrine hypertension

Armignacco

Reel

et al. 2022

Clin Epigenet

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“…miRNA-375 exerts its tumor-suppressive function by reducing the expression of metadherin (MTDH) and phosphorylation and cell viability depending on Akt-Ser473, regulating cell proliferation and viability ( 46 ). The reproducibility of studies to identify biomarker-circulating miRNAs has proved difficult for other conditions due to a series of technical challenges ( 47 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of the miRNA expression from the adipose tissue surrounding the adrenal neoplasia

Concistrè

Petramala

Circosta

et al. 2022

Front. Cardiovasc. Med.

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BackgroundPrimary aldosteronism (PA) is characterized by several metabolic changes such as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of non-coding small RNA molecules known to be critical regulators in several cellular processes associated with AT dysfunction. The aim of this study was to evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA) compared to the samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA).MethodsThe quantitative expression of selected miRNA using real-time PCR was analyzed in surrounding adrenal neoplasia, peri-renal, and subcutaneous AT samples of 16 patients with adrenalectomy (11 patients with APA and 5 patients with NFA).ResultsReal-time PCR cycles for miRNA-132, miRNA-143, and miRNA-221 in fat surrounding adrenal neoplasia and in peri-adrenal AT were significantly higher in APA than in patients with NFA. Unlike patients with NFA, miRNA-132, miRNA-143, miRNA-221, and miRNA-26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in patients with APA.ConclusionThis study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in patients with PA.

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“…In a systematic review, Spyroglou et al present recent developments in the transcriptomics, epigenetics and metabolomics of primary aldosteronism [ 4 ]. MicroRNAs belonging to the group of non-coding RNA molecules are also investigated as circulating markers in primary aldosteronism [ 5 ].…”

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confidence: 99%