Integrative discovery and targeted proteomics elucidate the plasma exosomal landscape in thyroid disorders, with emphasis on papillary thyroid carcinoma complicating Hashimoto’s thyroiditis

Introduction: Thyroid cancer represents the most prevalent malignancy of the endocrine system, with papillary thyroid carcinoma (PTC) accounting for approximately 90% of cases. Hashimoto's thyroiditis (HT) is a common benign thyroid disorder, frequently associated with structural alterations in thyroid morphology. Evidence indicated that HT may be a risk factor for the development of PTC. Exosomes promote intercellular communication by transferring proteins, mRNAs, micro-RNAs (miRNAs), and lipids to recipient cells, rendering them potential sources of disease-specific biomarkers. Methods: This study employed an integrative approach, combining exosome isolation, proteomics, and bioinformatics to identify plasma-derived exosomal biomarkers associated with PTC in the context of HT. Plasma samples were obtained from three patients each with PTC, PTC associated with HT (PTC-W), HT, and healthy controls (HCs). Exosomal proteins were extracted and analyzed using label-free quantitative proteomics. Results: A total of 45 differentially expressed proteins (DEPs) were identified between PTC-W and HT. Functional annotation and enrichment analyses revealed that these DEPs were predominantly implicated in extracellular matrix (ECM)-receptor interactions and immune response pathways. Subsequent validation via parallel reaction monitoring (PRM) confirmed that SVEP1 and IGKV3-7 exhibited consistent and statistically significant expression levels across discovery and validation phases. Discussion: These results highlight SVEP1 and IGKV3-7 as promising plasma exosomal biomarkers for PTC in patients with HT, providing mechanistic insights into the progression from HT to PTC and potential utility for non-invasive clinical diagnosis.