Comprehensive analysis of circulating microRNAs in plasma of patients with pituitary adenomas

Németh, Kinga, Ottó Darvasi, István Likó, Nikolette Szücs, Sándor Czirják, Lilla Reiniger, Borbála Szabó et al. "Comprehensive analysis of circulating microRNAs in plasma of patients with pituitary adenomas." The Journal of Clinical Endocrinology & Metabolism (2019).

Abstract

Background
Circulating miRNAs in pituitary adenoma would help patient care especially in non-functioning adenoma cases as minimally invasive biomarkers of tumor recurrence and progression.
Aim
Our aim was to investigate plasma miRNA profile in patients with pituitary adenoma.
Materials and Methods
149 plasma and extracellular vesicle (preoperative, early- and late postoperative) samples were collected from 45 pituitary adenoma patients. Adenomas were characterized based on anterior pituitary hormones and transcription factors by immunostaining. MiRNA next generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assay was used for validation on extended sample set. PA tissue miRNAs were evaluated by TaqMan array and literature data.
Results
Global downregulation of miRNA expression was observed in plasma samples of pituitary adenoma patients compared to normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples and normal controls. MiRNAs with altered expression in both plasma and different adenoma tissues were identified. 3, 7 and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in growth hormone secreting, FSH/LH+ and hormone-immunonegative groups, respectively. MiR-143-3p was downregulated in late- but not in early postoperative plasma samples compared to preoperative ones exclusively in FSH/LH+ adenomas. Plasma level of miR-143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (AUC=0.79; p=0.02).
Conclusions
Differentially expressed miRNAs in pituitary adenoma tissues have low abundance in plasma minimizing their role as biomarkers. Plasma miR-143-3p decreases in patients with FSH/LH+ adenoma indicated successful surgery, but its application for evaluating tumor recurrence needs further investigation.
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