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Circulating miRNA expression profiling in primary aldosteronism

ABSTRACT: Introduction: Primary aldosteronism (PA) is a major cause of secondary hypertension. The two principal forms of PA are bilateral adrenal hyperplasia (BAH) and aldosterone-producing adenoma (APA) whose differentiation is clinically pivotal, due to their different treatments. Adrenal venous sampling (AVS) is considered to be the gold standard for the differentiation of the two clinical entities, but it is invasive, requires great expertise and is unavailable in many centers. There would be a major clinical need for a reliable and easily accessible diagnostic biomarker. Circulating microRNA were shown to be useful as minimally invasive diagnostic markers in many diseases, but their potential applicability in PA has not yet been investigated. Aims: To determine and compare the circulating microRNA expression profiles of AVS-confirmed APA and BAH plasma samples, and to evaluate their applicability as minimally invasive markers. Methods: 81 AVS-confirmed plasma samples were included. Next-generation sequencing (NGS) was performed on 30 EDTA-anticoagulated plasma samples. Significantly differently expressed miRNAs were validated by real-time RT-qPCR on all samples. Results: We have found relative overexpression of miR-30e-5p, miR-30d-5p, miR-223-3p and miR-7-5p in BAH compared to APA by NGS. Validation of 81 samples confirmed significant overexpression (p=0.03) of miR-7-5p. Regarding the microRNA expressional variations, APA is more heterogenous at the miRNA level compared to BAH. Conclusion: miR-7-5p was significantly overexpressed in BAH samples compared to APA samples, but its sensitivity and specificity values are not good enough for introduction to the clinical practice yet.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126386 | GEO | 2019/02/12

REPOSITORIES: GEO

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Project description:We aimed at extending the repertoire of high-quality miRNA normalizers for reverse transcription-quantitative PCR (RT-qPCR) of human plasma with special emphasis on the extremely guanine-cytosine-rich portion of the miRNome. For high-throughput selection of stable candidates, microarray technology was preferred over small-RNA sequencing (sRNA-seq) since the latter underrepresented miRNAs with a guanine-cytosine (GC) content of at least 75% (p = 0.0002, n = 2). miRNA abundances measured on the microarray were ranked for consistency and uniformity using nine normalization approaches. The eleven most stable sequences included miRNAs of moderate, but also extreme GC content (45%–65%: miR-320d, miR-425-5p, miR-185-5p, miR-486-5p; 80%–95%: miR-1915-3p, miR-3656-5p, miR-3665-5p, miR-3960-5p, miR-4488-5p, miR-4497 and miR-4787-5p). In contrast, the seven extremely GC-rich miRNAs were not found in the two plasma miRNomes screened by sRNA-seq. Stem-loop RT-qPCR was employed for stability verification in 32 plasma samples of healthy male Caucasians (age range: 18–55 years). In general, inter-individual variance of miRNA abundance was low or very low as indicated by coefficient of variation (CV) values of 0.6%–8.2%. miR-3665 and miR-1915-3p outperformed in this analysis (CVs: 0.6 and 2.4%, respectively). The eight most stable sequences included four extremely GC-rich miRNAs (miR-1915-3p, miR-3665, miR-4787-5p and miR-4497). The best-performing duo normalization factor (NF) for the condition of human plasma, miR-320d and miR-4787-5p, also included a GC-extreme miRNA. In summary, the identification of extremely guanine-cytosine-rich plasma normalizers will help to increase accuracy of PCR-based miRNA quantification, thus raise the potential that miRNAs become markers for psychological stress reactions or early and precise diagnosis of clinical phenotypes. The novel miRNAs might also be useful for orthologous contexts considering their conservation in related animal genomes.

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Circulating miRNA expression profiling in primary aldosteronism

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