Comprehensive Analysis of Circulating miRNAs in the Plasma of Patients With Pituitary Adenomas

Abstract

Background Circulating miRNAs in pituitary adenomas would improve patient care, especially as minimally invasive biomarkers of tumor recurrence and progression in nonfunctioning adenoma cases. Aim Our aim was to investigate plasma miRNA profiles in patients with pituitary adenomas. Materials and Methods A total of 149 plasma and extracellular vesicle (preoperative, early postoperative, and late postoperative) samples were collected from 45 patients with pituitary adenomas. Adenomas were characterized on the basis of anterior pituitary hormones and transcription factors by immunostaining. miRNA next-generation sequencing was performed on 36 samples (discovery set). Individual TaqMan assays were used for validation on an extended sample set. Pituitary adenoma tissue miRNAs were evaluated by TaqMan array and data in the literature. Results Global downregulation of miRNA expression was observed in plasma samples of pituitary adenomas compared with normal samples. Expression of 29 miRNAs and isomiR variants were able to distinguish preoperative plasma samples from normal controls. miRNAs with altered expression in both plasma and different adenoma tissues were identified. Three, seven, and 66 miRNAs expressed differentially between preoperative and postoperative plasma samples in GH-secreting, FSH/LH+, and hormone-immunonegative groups, respectively. miR‒143-3p was downregulated in late postoperative but not in early postoperative plasma samples compared with preoperative ones exclusively in FSH/LH+ adenomas. The plasma level of miR‒143-3p discriminated these samples with 81.8% sensitivity and 72.3% specificity (area under the curve = 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 level decreased in patients with FSH/LH+ adenomas, indicating successful surgery, but its application for evaluating tumor recurrence needs further investigation.

Circulating miRNA Increases the Diagnostic Accuracy of Chromogranin A in Metastatic Pancreatic Neuroendocrine Tumors

“…Low abundance (<50 UMI read number) miRNAs were excluded from further analysis because these miRNAs could not be validated in our experimental set up [ 26 ]. 33 miRNAs differentiated pNET/PPGL patients from normal controls irrespective of PPI treatment ( Table 1 , Figure 1 D).…”

Biomarkers for Liquid Biopsies of Pituitary Neuroendocrine Tumors

“…The plasma levels of miR-143-3p were found to be significantly decreased exclusively in patients with gonadotropinomas after tumor removal. This resulted in an area under the ROC curve of 0.79, which grants this miRNA a diagnostic value for patient follow-up [86]. As this miRNA was also found to be reduced in early and late stages of colorectal tumors, it is assumed to be involved in tumor formation.…”

MiRNAs as Noninvasive Biomarkers and Therapeutic Agents of Pituitary Adenomas

“…RNA sequencing analysis of preoperative and late postoperative plasma samples collected 3 months after pituitary surgery have exhibited differential expression of miRNAs [ 47 ]. In this study, the patients of different groups with growth hormone (GH)-secretion, follicle-stimulating hormone (FSH)/luteinizing hormone (LH), and hormone-immunonegative (HN) groups are associated with differential expression of 3, 7, and 66 circulating miRNAs, respectively [ 47 ]. Next, circulating miRNAs with higher coverage for validation were selected from significant circulating miRNAs.…”