4.7 Article

The ElonginB/C-Cullin5-SOCS-Box-Complex Is a Potential Biomarker for Growth Hormone Disorders

Journal

BIOMEDICINES
Volume 9, Issue 2, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9020201

Keywords

acromegaly; growth hormone deficiency; biomarker; SOCS2; liquid biopsies; pituitary

Funding

  1. European Regional Development Fund (ERDF) [85000782]
  2. Pfizer
  3. Ipsen
  4. Novartis
  5. German Research Foundation
  6. Technische Hochschule Wildau-Technical University of Applied Sciences

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The combination of ECS-complex proteins SOCS2, cullin-5, and Rbx-2 can effectively identify patients with acromegaly or GHD, even in cases where IGF-1 levels are normal or no treatment has been received. SOCS2 exhibits the best diagnostic performance individually, while the combination of the three proteins shows perfect sensitivity and specificity for all patient groups and controls.
Insulin-like growth factor 1 (IGF-1) is the standard biochemical marker for the diagnosis and treatment control of acromegaly and growth hormone deficiency (GHD). However, its limitations necessitate the screening for new specific and sensitive biomarkers. The elonginB/C-cullin5-SOCS-box-complex (ECS-complex) (an intracellular five-protein complex) is stimulated by circulating growth hormone (GH) and regulates GH receptor levels through a negative feedback loop. It mediates the cells' sensitivity for GH and therefore, represents a potent new biomarker for those diseases. In this study, individual ECS-complex proteins were measured in whole blood samples of patients with acromegaly (n = 32) or GHD (n = 12) via ELISA and compared to controls. Hierarchical clustering of the results revealed that by combining the three ECS-complex proteins suppressor of cytokine signaling 2 (SOCS2), cullin-5 and ring-box protein 2 (Rbx-2), 93% of patient samples could be separated from controls, despite many patients having a normal IGF-1 or not receiving medical treatment. SOCS2 showed the best individual diagnostic performance with an overall accuracy of 0.93, while the combination of the three proteins correctly identified all patients and controls. This resulted in perfect sensitivity and specificity for all patient groups, which demonstrates potential benefits of the ECS-complex proteins as clinical biomarkers for the diagnostics of GH-related diseases and substantiates their important role in GH metabolism.

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