Identification of Thyroid-Associated Serum microRNA Profiles and Their Potential Use in Thyroid Cancer Follow-Up

CONTEXT: Trends toward more conservative management of papillary thyroid cancer (PTC) diminish the primacy of serum thyroglobulin (Tg) assays as a posttreatment surveillance tool. OBJECTIVE: To identify thyroid tumor-associated microRNAs (miRNAs) in the serum with potential for development as unique biomarkers of PTC recurrence. METHODS: We measured expression of 754 miRNAs in serum samples collected from 11 patients with PTC before and 30 days after thyroidectomy. Major candidates were then re-evaluated by absolute quantitative polymerase chain reaction analysis in an independent cohort of patients with PTC (n = 44) or benign nodules and 20 healthy controls (HCs). The 2 miRNAs most significantly associated with thyroid tumors were then assessed in matched serum samples (before and 30 days and 1 to 2 years after surgery) from the 20 PTC patients with complete follow-up datasets and results correlated with American Thyroid Association (ATA) responses to therapy. RESULTS: Eight miRNAs (miR-221-3p, miR-222-3p, miR-146a-5p, miR-24-3p, miR-146b-5p, miR-191-5p, miR-103a-3p, and miR-28-3p) displayed levels in prethyroidectomy serum samples from patients with PTC that significantly exceeded those measured after thyroidectomy and those found in samples from HCs. The 2 most promising candidates-miR-146a-5p and miR-221-3p -were further analyzed in the 20 PTC patients mentioned earlier. Serum levels of both miRNAs after 1 to 2 years of follow-up were consistent with ATA responses to therapy in all patients, including 2 with structural evidence of disease whose Tg assays remained negative (<1 ng/mL). CONCLUSION: miR-146a-5p and miR-221-3p hold remarkable promise as serum biomarkers for post-treatment monitoring of PTC patients, especially when Tg assay results are uninformative.