Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism.

Samira Mercedes Sadowski, Marc Pusztaszeri, Marie-Claude Brulhart-Meynet, Volodymyr Petrenko, Claudio De Vito, Jonathan Sobel, Céline Delucinge-Vivier, Electron Kebebew, Romano Regazzi, Jacques Philippe, Frédéric Triponez, Charna Dibner

Journal: The Journal of clinical endocrinology and metabolism 2018;103(6):2189-2198

PMID: 29659895

Full Text on Ovid Technologies, Inc. View on PubMed

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 (PGs) in sporadic primary (HPT1) and secondary hyperparathyroidism (HPT2).

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, adenomatous, HPT1, and HPT2 hyperplastic PG formalin-fixed paraffin-embedded samples were subjected to NanoString analysis. In silico microRNA (miRNA) analyses and messenger RNA-miRNA network in PG pathologies were conducted. Individual messenger RNA 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 with normal PG tissue when assessed by NanoString and quantitative reverse transcription polymerase chain reaction. RET was affected in HPT1 hyperplasia, whereas CaSR and VDR transcripts were downregulated in HPT2 hyperplastic PG tissue. CDH1, c-MET, MYC, and CaSR were altered in adenoma compared with 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 these genes, did not exhibit a clear tendency upon experimental validation.

CONCLUSIONS

The presented gene expression analysis provides a differential molecular characterization of PG adenoma and hyperplasia pathologies, advancing our understanding of their etiology.

Address: Department of Thoracic and Endocrine Surgery, University Hospitals of Geneva and Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Division of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland.; Department of Pathology, Jewish General Hospital and McGill University, Montreal, Canada.; Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospitals of Geneva, Geneva, Switzerland.; Diabetes Centre, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Division of Endocrinology, Diabetes, Hypertension and Nutrition, University Hospitals of Geneva, Geneva, Switzerland.; Diabetes Centre, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; iGE3 Genomics Platform, University of Geneva, Geneva, Switzerland.; Department of Cell Physiology and Metabolism, Faculty of Medicine, University of Geneva, Geneva, Switzerland.; Division of Clinical Pathology, University Hospitals of Geneva, Geneva, Switzerland.; Department of Fundamental Neurosciences, University of Lausanne, Lausanne, Switzerland.; iGE3 Genomics Platform, University of Geneva, Geneva, Switzerland.; Department of Surgery, Stanford University, California.

DOI: 10.1210/jc.2017-02506