Identification of Differential Transcriptional Patterns in Primary and Secondary Hyperparathyroidism

Autor: Céline Delucinge-Vivier, Electron Kebebew, Samira M. Sadowski, Marie-Claude Brulhart-Meynet, Frédéric Triponez, Marc Pusztaszeri, Jonathan Sobel, Claudio De Vito, Volodymyr Petrenko, Charna Dibner, Jacques Philippe, Romano Regazzi
Rok vydání: 2018
Předmět:
Adenoma
0301 basic medicine
medicine.medical_specialty
endocrine system diseases
Transcription
Genetic
Endocrinology
Diabetes and Metabolism
Clinical Biochemistry
Gene Expression
ddc:616.07
Biology
Biochemistry
Calcitriol receptor
Parathyroid Glands
Proto-Oncogene Proteins c-myc
03 medical and health sciences
Endocrinology
Internal medicine
Gene expression
medicine
Humans
ddc:616
Hyperparathyroidism
Tissue Inhibitor of Metalloproteinase-1
ddc:617
Biochemistry (medical)
Period Circadian Proteins
Proto-Oncogene Proteins c-met
Hyperplasia
Hyperparathyroidism
Primary
medicine.disease
Reverse transcription polymerase chain reaction
Basic-Leucine Zipper Transcription Factors
Parathyroid Neoplasms
030104 developmental biology
Cancer research
Parathyroid hormone secretion
Hyperparathyroidism
Secondary
Secondary hyperparathyroidism
hormones
hormone substitutes
and hormone antagonists
Zdroj: Journal of Clinical Endocrinology and Metabolism (2018)
ISSN: 1945-7197
0021-972X
DOI: 10.1210/jc.2017-02506
Popis: 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.
Databáze: OpenAIRE
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