Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism.

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Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism.

J Clin Endocrinol Metab. 2018 Apr 05;:

Authors: Sadowski SM, Pusztaszeri M, Brulhart-Meynet MC, Petrenko V, De Vito C, Sobel J, Delucinge-Vivier C, Kebebew E, Regazzi R, Philippe J, Triponez F, Dibner C

Abstract
Context: Hyperparathyroidism is associated with hypercalcemia and the excess of parathyroid hormone secretion. However, the alterations in molecular pattern of functional genes during parathyroid tumorigenesis have not been unraveled. We aimed at establishing transcriptional patterns of normal and pathological parathyroid glands (PG) in sporadic primary and secondary hyperparathyroidism (HPT1, 2).
Objective: To evaluate dynamic alterations in molecular patterns as a function of the type of PG pathology, a comparative transcript analysis was conducted in subgroups of healthy samples, sporadic HPT1 adenoma and hyperplasia, and HPT2.
Design: Normal, adenoma, HPT1 and HPT2 hyperplasia PG formalin-fixed paraffin-embedded (FFPE) samples were subjected to NanoString analysis. In silico microRNA analyses and mRNA-miRNA network in PG pathologies were conducted. Individual mRNA and miRNA levels were assessed in snap-frozen PG samples.
Results: The expression levels of c-MET, MYC, TIMP1, and clock genes NFIL3 and PER1 were significantly altered in HPT1 adenoma compared to normal PG tissue when assessed by NanoString and qRT-PCR. RET was affected in HPT1 hyperplasia, while CaSR and VDR transcripts were downregulated in HPT2 hyperplastic PG tissue. CDH1, c-MET and MYC and CaSR were altered in adenoma as compared to hyperplasia. Correlation analyses suggest that c-MET, MYC and NFIL3 exhibit collective expression level changes associated with HPT1 adenoma development. miRNAs, predicted in silico to target the above genes, did not exhibit a clear tendency upon experimental validation.
Conclusions: The presented gene expression analysis provides the first differential molecular characterization of PG adenoma and hyperplasia pathologies, advancing our understanding of their etiology.

PMID: 29659895 [PubMed - as supplied by publisher]

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