Targeted Proteomics Reveals Novel Biomarkers of Disease Activity and Inflammation in Acromegaly

OBJECTIVE: Biochemical diagnostic approach for acromegaly relies heavily on the two biomarkers, growth hormone (GH) and insulin like growth factor 1 (IGF1), known to be dynamically affected, and influencing diagnostic accuracy. We sought to identify disease-specific biomarkers to improve diagnostic and disease activity monitoring and add insight into systemic effects of chronic GH/IGF1 excess. METHODS: Thirty-seven patients diagnosed with acromegaly were enrolled. A sub-cohort (n=14) of these received primary somatostatin receptor ligand (SRL) treatment before surgery. Plasma samples collected at baseline, preoperative medical treatment and postoperative visits, were used to perform proteomic analysis of 184 proteins, with Olink Target 96 Cardiovascular III and Inflammation panels. Eight proteins were validated Enzyme Immunoassay (EIA). Dual-energy X-ray absorptiometry and biochemical measurements were performed at all visits. RESULTS: A total of 37 proteins were significantly differentially expressed (p-adjusted <.05) before and after disease control by surgery. Several proteins correlated with GH and IGF1. Interestingly, a strong correlation between some proteins and lean body mass, but not total adipose tissue, was observed. Strong correlation was observed between Olink and EIA measured protein levels. Enrichment analyses revealed five clusters, with extracellular matrix (ECM) remodeling and inflammation being most prominent. In addition, five proteins showed a temporal change with SRL treatment. CONCLUSIONS: Acromegaly is associated with changes in ECM remodeling and inflammation. Several proteins were linked to disease activity, with glial cell derived neurotrophic factor and insulin like growth factor binding protein 2 serving as promising plasma biomarkers with potential to further optimize management of disease.