Abstract
The diagnosis of lymph node metastasis (LNM) by liquid biopsy is a novel concept prompted by the necessity to develop a more convenient and accurate method to guide the clinical management of early LNM in papillary thyroid carcinoma (PTC). However, the sensitivity and specificity of many biomarkers are not high enough. We aimed to detect circRNAs from peripheral circulation that may be better associated with the prognosis of LNM in PTC. First, Galectin-3 (Gal3) in blood was determined to be highly expressed in LNM patients. Second, based on a bioinformatics analysis and miRNA sequencing analysis from 2 paired primary and LNM tumors, miR-873 was identified to directly target Gal3, which was significantly associated with clinical parameters including LNM. Third, from additional circRNA sequencing, circRNA-UMAD1 was selected as a specific sponge for miR-873 and was correlated with Gal3 levels in peripheral circulation. Fourth, circRNA-UMAD1 and Gal3 were identified to have stronger co-biomarker potential with relatively high expression in the serum of LNM patients compared with primary tumor patients, as demonstrated by the RNA expression levels in the serum of 50 PTC patients with or without LNM by quantitative real-time PCR. Overall, the combination of circRNA-UMAD1 and Gal3 is a useful and effective co-biomarker for the prognosis of LNM in PTC patients. This new molecular typing method for LNM in PTC is more precise.