Shujun Xia,1 Chuandong Wang,2 Emily Louise Postma,3 Yanhua Yang,1 Xiaofeng Ni,1 Weiwei Zhan1 1Ultrasound Department, RuiJin Hospital, Shanghai Jiao Tong University School of Medicine, 2Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Jiao Tong University School of Medicine (SJTUSM) and Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai, China; 3Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands Abstract: Lymph node metastasis (LNM) is common in papillary thyroid cancer (PTC), and is an indicator of recurrence. The detailed molecular mechanism of LNM in PTC has not been well described. This study aimed to investigate the role of fibronectin 1 in PTC LNM and its clinical relevance. The expression of fibronectin 1 was confirmed in PTC tissues and cell lines. A correlation analysis was conducted and a receiver-operating characteristic curve obtained. The effect of fibronectin 1 on the proliferation of PTC cell lines was performed using a colony-formation assay and Cell Counting Kit 8. Cell-cycle analysis was performed with a flow-cytometry assay. Migration and invasion ability were evaluated by transwell and wound-healing assays. Fibronectin 1 was overexpressed in metastasized PTC. Overexpressed fibronectin 1 was positively correlated with PTC LNM. Receiver-operating characteristic analysis showed that the diagnostic accuracy of fibronectin 1 was 81.1%, with sensitivity of 80% and specificity of 82%. Overexpression of fibronectin 1 promoted proliferation, migration, and invasion in PTC. Fibronectin 1 plays a critical role in PTC metastasis by modulating the proliferation, migration, and invasion ability of PTC cells, and it is a valuable diagnostic biomarker for predicting PTC LNM. Keywords: fibronectin 1, papillary thyroid cancer, lymph node metastasis, diagnostic biomarker