Abstract
Approximately 85% of histological subtypes of thyroid cancer are papillary thyroid cancer (PTC), and the morbidity and mortality of PTC patients rapidly increased due to lymph node metastases or distant metastasis. Therefore, it needs to distill an enhanced understanding of the pathogenesis of PTC patients with lymph node metastases or distant metastasis. We employed the TMT-based quantitative proteomics approach to identify and analyze differentially expressed proteins in PTC with different degrees of lymph node metastases. Compared with paired normal tissues, asporin is overexpressed in PTC-N0, PTC-N1a, and PTC-N1b tumorous tissues via proteomics, western blotting, and immunohistochemistry assays. Functionally, asporin is mainly expressed in the extracellular matrix, cell membrane, and cytoplasm of PTC tumorous tissues, and promotes thyroid cancer cell proliferation, migration, and invasion. Mechanistically, asporin, interacting with HER2, co-localizes HER2 on the cell membrane and cytoplasm, and the asporin/HER2/SRC/EGFR axis upregulate the expression of EMT-activating transcription factors through the MAPK signaling pathway. Clinically, asporin can be regarded as a serological biomarker to identify PTC patients with or without lymph node metastasis, and high expression of asporin in PTC tumorous tissues is a risk factor for poor prognosis.