Abstract
MicroRNAs (miRNAs) are dysregulated in many tumors; however, miRNA regulation in parathyroid tumors remains poorly understood. To identify differentially expressed miRNAs between sporadic and hereditary parathyroid tumors and to analyze their correlation with clinicopathological features, a microarray containing 887 miRNAs was performed; then, the differentially expressed miRNAs were validated by qRT-PCR using 25 sporadic and 12 hereditary parathyroid tumors and 24 normal parathyroid tissue samples. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the utility of the miRNAs for distinguishing parathyroid tumor types. Compared to the miRNAs in the normal parathyroid tissues, 10 miRNAs were differentially expressed between the sporadic and hereditary parathyroid tumors. Seven of these miRNAs (let-7i, miR-365, miR-125a-3p, miR-125a-5p, miR-142-3p, miR-193b, and miR-199b-5p) were validated in the parathyroid tumor samples. Among these miRNAs, only miR-199b-5p was differentially expressed (P < 0.001); miR-199b-5p was significantly downregulated and negatively associated with PTH levels (γ = −0.579, P = 0.002) in the sporadic tumors but was upregulated in the hereditary tumors. This miRNA showed 67% sensitivity and 100% specificity for distinguishing sporadic and hereditary parathyroid tumors. These results reveal altered expression of a miRNA between sporadic and hereditary parathyroid tumors and the potential role of miR-199b-5p as a novel biomarker for distinguishing these two types of parathyroid tumors.
Highlights
Primary hyperparathyroidism (PHPT) is a relatively common endocrine disease with a prevalence of three per one thousand in the general population[1]
Four miRNAs, including miR-365, miR-125a-3p, miR-574-5p, and miR-1246, were significantly downregulated in sporadic parathyroid tumors, whereas miR-142-3p, let-7i, miR-125a-5p, miR-199b-5p, and miR-1274b_v16.0 were significantly upregulated; miR-193b was downregulated in multiple endocrine neoplasia type 1 (MEN1) parathyroid tumors
Even gene array data showed that hereditary parathyroid tumors are clustered with the sporadic form, indicating that these tumors may share a similar genetic pathway of tumorigenesis[26]
Summary
Primary hyperparathyroidism (PHPT) is a relatively common endocrine disease with a prevalence of three per one thousand in the general population[1]. PHPT shows the highest penetrant expression in this syndrome; PHPT occurs in almost 100% of MEN1 patients by the age of 50 yrs, while the MEN1 frequency in PHPT patients is estimated to be 1–18%4 Clinical features, such as age of onset, sex ratio, severity of bone involvement and recurrence rates after parathyroidectomy, are different between sporadic and hereditary parathyroid tumors[5,6]. The discrimination of these tumor types is important because the treatment and disease courses are quite different[7,8]. We determined whether miRNA profiling could serve as a potential biomarker for distinguishing these tumor types
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