Introduction: Graves disease and toxic multinodular goiter are known to have different etiologies and pathogenesis, which are not fully comprehended today. This study compares the protein profiles of Graves disease and toxic multinodular goiter patients thyroid samples using proteomics methods and investigates the role of differentiating proteins in the pathogenesis of these diseases.
Methods and Design: Difference Gel Electrophoresis (DIGE) was applied to protein extracts of thyroid samples from 12 patients with Graves disease and 12 patients with toxic multinodular goiter. Spots with differential expression were revealed by imaging and the proteins were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI TOF) followed by MASCOT search. They were classified on the basis of their functions in metabolic pathways by using Ingenuity Pathways Analysis (IPA).
Results: Difference Gel Electrophoresis images were analysed via PDQest Advance software and 330±20 protein spots were detected from the two group of gels. Of these spots, 23 displayed difference in their expressions between Graves disease and toxic multinodulary goiter samples. These were Prelamin A/C (LMNA), Macrophage capping protein (CAPG), alpha enolase 1 (ENO1), Rho GDP-dissociation inhibitor 1 (ARHGDIA), Peroxiredoxin 2 (PRDX2), Cathepsin B (CTSB), Cathepsin D (CTSD), Apolipoprotein A1 (APOA1), Heat shock protein β1 (HSP β1), Selenium-binding protein 1 (SELENBP1), Creatine kinase B (CKB), Succinyl-KoA:3-ketoacid Coenzyme A transferase 1(OXCT1), Dihidrolipoil dehydrogenase (DLD), Carbonic anhydrase (CA1), Triosephosphate isomerase (TPI1). Ingenuity Pathways Analysis revealed that some of these proteins have functions related to cell proliferation and they were also associated with malignities such as pancreas tumor, hepatocellular carcinoma and colorectal carcinoma.
Conclusion: Although our findings are preliminary, they hold importance by providing the first comprehensive comparative proteomics data about Graves disease vs toxic multinodular goiter.