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

内容摘要

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. 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. 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. 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.