Targeted Proteomics Identifies GDNF and IGFBP2 as Novel Plasma Biomarkers for Acromegaly Disease Activity and Inflammation
Background
The current biochemical diagnosis and monitoring of acromegaly heavily relies on measuring growth hormone (GH) and insulin-like growth factor 1 (IGF-1). However, these biomarkers are dynamically affected by various factors, leading to assay variability and potential discordance, which complicates the accurate assessment of disease activity. This variability can hinder precise treatment adjustments and understanding of the systemic impact of chronic GH/IGF-1 excess. Identifying novel, stable, and disease-specific biomarkers is crucial to improve diagnostic accuracy, enhance disease activity monitoring, and provide deeper insights into the broader systemic effects of this condition.
Study Design
Researchers enrolled 37 patients diagnosed with acromegaly. A sub-cohort (n = 14) received primary somatostatin receptor ligand (SRL) treatment before surgery. Plasma samples were collected at baseline, during preoperative medical treatment, and at postoperative visits. These samples underwent proteomic analysis using Olink Target 96 Cardiovascular III and Inflammation panels to quantify 184 proteins. Eight proteins were subsequently validated using Enzyme Immunoassay (EIA). Additionally, Dual-energy X-ray absorptiometry (DXA) and other biochemical measurements were performed at all visits to correlate protein changes with clinical parameters.
Results
A total of 37 proteins were found to be significantly differentially expressed (P-adjusted < .05) in patients before and after achieving disease control through surgery. Several of these proteins demonstrated strong correlations with both GH and IGF-1 levels. Interestingly, a robust correlation was observed between some proteins and lean body mass, but not with total adipose tissue. The study also confirmed a strong correlation between protein levels measured by Olink and those validated by EIA. Enrichment analyses revealed 5 distinct protein clusters, with extracellular matrix (ECM) remodeling and inflammation pathways being the most prominent and significantly altered in acromegaly. Furthermore, 5 specific proteins exhibited a temporal change in response to somatostatin receptor ligand (SRL) treatment.
Glial cell derived neurotrophic factor (GDNF) and insulin like growth factor binding protein 2 (IGFBP2) were highlighted as particularly promising plasma biomarkers, showing strong links to acromegaly disease activity and systemic inflammation.
Key Findings
- 37 proteins were significantly differentially expressed after surgical disease control (P-adjusted < .05).
- Glial cell derived neurotrophic factor (GDNF) and insulin like growth factor binding protein 2 (IGFBP2) were identified as promising plasma biomarkers.
- Protein changes correlated with GH, IGF-1, and lean body mass.
- Enrichment analysis revealed
extracellular matrix (ECM) remodelingandinflammationas prominent pathways. - 5 proteins showed temporal changes in response to somatostatin receptor ligand (SRL) treatment.
Why It Matters
This research significantly advances the potential for more precise and reliable monitoring of acromegaly disease activity. By identifying novel biomarkers like GDNF and IGFBP2, clinicians may eventually have tools that are less susceptible to the dynamic fluctuations and assay variability seen with traditional GH and IGF-1 measurements. This could lead to earlier and more accurate diagnosis, better assessment of treatment response, and potentially more personalized therapeutic strategies. The insights into ECM remodeling and inflammation also broaden our understanding of acromegaly's systemic impact beyond just tumor growth, suggesting new targets for intervention. While these findings are promising, further validation in larger, independent cohorts is essential before these biomarkers can be integrated into routine clinical protocols.
acromegaly
biomarkers
proteomics
inflammation
ecm-remodeling
gh