Comparative Gene Expression Profiles in Parathyroid Adenoma and Normal Parathyroid Tissue.

Young Chai,Seongmin Choi,Kyu Lee,Heejoon Chae,Heonyi Lee,Kwangsoo Kim,Sang Kim

doi:10.3390/jcm8030297

Abstract

Parathyroid adenoma is the main cause of primary hyperparathyroidism, which is characterized by enlarged parathyroid glands and excessive parathyroid hormone secretion. Here, we performed transcriptome analysis, comparing parathyroid adenomas with normal parathyroid gland tissue. RNA extracted from ten parathyroid adenoma and five normal parathyroid samples was sequenced, and differentially expressed genes (DEGs) were identified using strict cut-off criteria. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using DEGs as the input, and protein-protein interaction (PPI) networks were constructed using Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and visualized in Cytoscape. Among DEGs identified in parathyroid adenomas (n = 247; 45 up-regulated, 202 down-regulated), the top five GO terms for up-regulated genes were nucleoplasm, nucleus, transcription DNA-template, regulation of mRNA processing, and nucleic acid binding, while those for down-regulated genes were extracellular exosome, membrane endoplasmic reticulum (ER), membrane, ER, and melanosome. KEGG enrichment analysis revealed significant enrichment of five pathways: protein processing in ER, protein export, RNA transport, glycosylphosphatidylinositol-anchor biosynthesis, and pyrimidine metabolism. Further, PPI network analysis identified a densely connected sub-module, comprising eight hub molecules: SPCS2, RPL23, RPL26, RPN1, SEC11C, SEC11A, RPS25, and SEC61G. These findings may be helpful in further analysis of the mechanisms underlying parathyroid adenoma development.

Highlights

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by inappropriate excessive secretion of parathyroid hormone (PTH) and consequent hypercalcemia [1,2]
Somatic mutations in genes associated with hyperparathyroidism, including MEN1, CASR, AP2S1, GNA11, CDC73, CDKN1A, CDKN1B, CDKN2C, RET, PTH, CCND1, AIP, CTNNB1, EZH2, ZFX, CDC73, and FGF23, were not detected in either parathyroid adenoma or normal parathyroid tissues
Genes Differentially Expressed between PHPT and Normal Parathyroid Tissue

Summary

Introduction

Primary hyperparathyroidism (PHPT) is a common endocrine disease characterized by inappropriate excessive secretion of parathyroid hormone (PTH) and consequent hypercalcemia [1,2]. PHPT is more common in women than men, those ≥ 45 years old; the ratio of incidence in women to men is almost 2:1 [3], and PHPT incidence increases rapidly with age. The most common cause of PHPT is sporadic parathyroid adenoma, which accounts for 85% of PHPT. Various hereditary types of hyperparathyroidism are caused by mutations of specific genes, including: multiple endocrine neoplasia type 1 and familial isolated hyperparathyroidism, caused by alterations in the MEN1 gene; familial hypercalcemia with hypercalciuria, attributable to CASR gene changes; and hyperparathyroidism-jaw tumor syndrome and familial isolated hyperparathyroidism, caused by HRP2 gene mutations [8,9,10]

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Results

Conclusion