Introduction: Despite recent developments in biochemical, radiological and molecular techniques, a preoperative diagnosis of parathyroid carcinoma (PC) remains a difficult task. The main challenge of all studies in this area is a small number of cases based on retrospective data. The search for new blood biomarkers associated with PC could be important for early diagnosis and prognosis. Dysregulated microRNA (miRNA) levels are involved in tumorigenesis and may serve as diagnostic markers for PC.
Objective: To define specific miRNAs that can be used for differential diagnosis of PC.
Materials and methods: Serum samples were taken from patients with biochemically confirmed symptomatic primary hyperparathyroidism and frozen at −20 °C. After the parathyroidectomy the patients were divided into 2 groups based on the results of morphological analysis: patients with PC (n=12) and patients with PA (n=12) matched by age, sex, level of PTH and calcium. Total RNA isolation from plasma samples with on-column digestion of the genomic DNA was carried out with mirVana PARIS Kit (Ambion). Reverse transcription was carried out using a TaqMan MicroRNA Reverse Transcription Kit (Applied Biosystems). To examine differential expression of 760 endogenous miRNAs, Real-Time PCR was performed on QuantStudio 12 K Flex station (Life Technologies) with TaqMan OpenArray Real-Time PCR Master Mix and TaqMan OpenArray Human MicroRNA Panel (Applied Biosystems). The data obtained were analyzed using Expression Suite Software v.1.1 (Applied Biosystems). MiRNAs in a PC group whose expression differed more than two times from the control PA group (P=< 0.05) were selected for subsequent analysis.
Results: We identified 10 miRNAs whose levels were significantly lower in PC group compared to PA (control) group: miRNA-342-3p (P=0.000), miR-195 (P=0.021), miRNA let-7e (P=0.049), miRNA-744 (P=0.024), miRNA-150 (P=0.028), miRNA-19a (P=0.037), miRNA-320 (P=0.047), miRNA-16 (P=0.024), miRNA-339-5p (P=0.05) and miRNA-361 (P=0.046); among those, downregulation of miRNA-342-3p (fold change =0.35) also met the Benjamini-Hochberg adjustment criteria for multiple comparisons. In addition, some studies have showed, that miRNA-342-3p regulates the carcinogenesis of various types of cancers such as liver cancer, cervical cancer, and NSCLC and its overexpression inhibits the proliferation, migration and cell invasion.
Conclusions: Our study demonstrates that serum miRNA-342-3p is a promising preoperative diagnostic biomarker for distinguishing PC from PA. We plan to improve the differential expression analysis of the selected miRNAs with a larger number of samples in the future.
18 - 21 May 2019
European Society of Endocrinology