Serum small extracellular vesicles-derived BST2 as a biomarker for papillary thyroid microcarcinoma promotes lymph node metastasis

Papillary thyroid microcarcinoma (PTMC), although frequently indolent, could be aggressive in a few patients, leading to lymph node metastasis (LNM) and worsened prognosis. To explore the role of protein profiling of small extracellular vesicles (sEVs) in the auxiliary diagnosis and risk stratification of PTMC, proteins in serum sEVs isolated from PTMC patients with (N = 10) and without (N = 10) LNM and benign thyroid nodule (BN) patients (N = 9) were profiled via a bioinformatics-integrated data-independent acquisition proteomic technique. The performance of candidate proteins as diagnostic and prognostic biomarkers in PTMC was assessed via receiver operating characteristic analysis. We found that serum sEVs from PTMC patients promoted the proliferation and migration of human papillary thyroid cancer (PTC) cells and tube formation in human lymphatic endothelial cells (HLECs). SEV proteins from PTMC patients with and without LNM have differential expression profiles, with bone marrow stromal cell antigen 2 (BST2) being best associated with PTMC progression. Through knockdown and overexpression, we proved that the high expression of sEV-derived BST2 was bound up with higher proliferation and migration ability of PTC cells as well as stronger lymphangiogenesis in HLECs. This study brought insight into the differential sEV-protein profile with or without LNM in PTMC. The serum sEV-BST2 may contribute to PTMC progression and LNM and may have diagnostic, prognostic, and therapeutic implications.