Abstract
OBJECTIVE: To develop a practical and cost-effective test to distinguish patients with malignant thyroid nodules eligible for active surveillance from those requiring immediate surgery. METHODS: This prospective observational study included patients with malignant thyroid nodules (3 to 15 mm) who were assigned to either an Active Surveillance Group (n = 30) or a Surgery Group (n = 21) based on the institutional protocol. The Surgery Group was further stratified according to the American Thyroid Association risk of recurrence/persistence. Preoperative serum levels of miR-146b-5p and miR-204, normalized to miR-16, were analyzed. Receiver operating characteristic curves were used to establish cut-off values to differentiate between low and intermediate/high risk of recurrence/persistence, which were subsequently applied to the Active Surveillance Group. RESULTS: Patients were initially assigned to the active surveillance (n = 30; 53.5 ± 12.6 years old) or Surgery Group (n = 21; 41.9 ± 7.9 years old). The mean follow-up duration for the Active Surveillance Group was 36.4 ± 25.8 months, during which no patients experienced disease progression. Five patients in the Active Surveillance Group were subsequently transitioned to the Surgery Group. Molecular analysis of the Surgery Group indicated that upregulation of miR-146b-5p/miR-16 and downregulation of miR-204/miR-16 were significantly associated with intermediate/high risk of recurrence/persistence (p = 0.005 and 0.006, respectively). Downregulation of miR-204/miR-16 demonstrated a sensitivity of 75% and a negative predictive value of 86.7%. The combination of upregulation of miR-146b-5p/miR-16 and downregulation of miR-204/miR-16 yielded both a specificity and negative predictive value of 100%. CONCLUSION: Decision-making for patients with low-risk papillary thyroid carcinoma regarding eligibility for active surveillance can be facilitated through serum analysis of miR-204/miR-16 expression, which may be used as a rule-out test. In contrast, combined analysis of miR-146b-5p/miR-16 and miR-204/miR-16 can serve as a rule-in test.