Endocrinol Metab.  2024 Apr;39(2):375-386. 10.3803/EnM.2023.1827.

Protein Signatures of Parathyroid Adenoma according to Tumor Volume and Functionality

• Kong SH
• Bae JM
• Kim JH
• Kim SW
• Han D
• Shin CS

• KMID: 2554642
• DOI: http://doi.org/10.3803/EnM.2023.1827

Abstract

Background
Parathyroid adenoma (PA) is a common endocrine disease linked to multiple complications, but the pathophysiology of the disease remains incompletely understood. The study aimed to identify the key regulator proteins and pathways of PA according to functionality and volume through quantitative proteomic analyses.
Methods
We conducted a retrospective study of 15 formalin-fixed, paraffin-embedded PA samples from tertiary hospitals in South Korea. Proteins were extracted, digested, and the resulting peptides were analyzed using liquid chromatography-tandem mass spectrometry. Pearson correlation analysis was employed to identify proteins significantly correlated with clinical variables. Canonical pathways and transcription factors were analyzed using Ingenuity Pathway Analysis.
Results
The median age of the participants was 52 years, and 60.0% were female. Among the 8,153 protein groups analyzed, 496 showed significant positive correlations with adenoma volume, while 431 proteins were significantly correlated with parathyroid hormone (PTH) levels. The proteins SLC12A9, LGALS3, and CARM1 were positively correlated with adenoma volume, while HSP90AB2P, HLA-DRA, and SCD5 showed negative correlations. DCPS, IRF2BPL, and FAM98A were the main proteins that exhibited positive correlations with PTH levels, and SLITRK4, LAP3, and AP4E1 had negative correlations. Canonical pathway analysis demonstrated that the RAN and sirtuin signaling pathways were positively correlated with both PTH levels and adenoma volume, while epithelial adherence junction pathways had negative correlations.
Conclusion
Our study identified pivotal proteins and pathways associated with PA, offering potential therapeutic targets. These findings accentuate the importance of proteomics in understanding disease pathophysiology and the need for further research.

Keyword

Parathyroid; Adenoma; Proteins; Parathyroid hormone; Volume

Figure

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  Fig. 1. Schematic process of proteomics analysis. FFPE, formalin-fixed and paraffin-embedded; LC-MS/MS, liquid chromatography-tandem mass spectrometry.

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  Fig. 2. Volcano plots of proteins significantly associated with (A) tumor volume and (B) parathyroid hormone (PTH) levels. Top 10 proteins are highlighted in blue (negative correlation) or red (positive correlation).

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  Fig. 3. A heatmap of canonical pathways using the activation Z-score of statistically significantly enriched pathways for volume and parathyroid hormone (PTH).

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  Fig. 4. Protein networks of upstream regulators according to (A) tumor volume and (B) parathyroid hormone (PTH) levels, and (C) a Venn diagram of upstream regulators and key transcriptional factors.

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