Dynamic monitoring of circulating microRNAs as a predictive biomarker for the diagnosis and recurrence of papillary thyroid carcinoma

摘要

Circulating microRNAs (miRNAs/miRs) are considered to be potential biomarkers for numerous types of cancer. However, previous investigations into the expression of miRNAs in the serum of patients with papillary thyroid carcinoma (PTC) to predict diagnosis, prognosis and recurrence have reported conflicting results, and the role of miRNAs remains unclear. The present study dynamically assessed the circulating miRNA profile in patients with PTC and determined whether miRNAs in the serum could be used as biomarkers for the diagnosis, prognosis and recurrence of PTC. The expression levels of 3 reportedly upregulated miRNAs (miR-222, miR-221 and miR-146b) were analyzed using reverse transcription-quantitative polymerase chain reaction in 106 patients with PTC, 35 patients with benign thyroid nodules (BTN) and 40 paired controls. Patients with either newly diagnosed PTC or BTN who were undergoing thyroidectomies were recruited for a dynamic analysis of preoperative and postoperative serum miRNA levels. The results indicated that the expression levels of serum miR-222, miR-221 and miR-146b were significantly increased in patients with newly diagnosed PTC compared with controls and patients with BTN. Receiver operating characteristic curve analysis indicated that these miRNAs had a high diagnostic sensitivity and specificity for PTC prior to surgery. The expression of these three miRNAs in serum was significantly associated with poorer prognostic variables, including extrathyroidal invasion, metastatic lymph nodes and high-risk or advanced tumor node metastasis stage. More notably, the present study identified 2.36-, 2.69- and 5.39-fold reductions in the serum levels of miR-222, miR-221 and miR-146b, respectively, subsequent to patients undergoing a thyroidectomy. In addition, miR-222, miR-221 and miR-146b were overexpressed in the PTC with recurrence group compared with the PTC without recurrence group. Collectively, dynamic monitoring of circulating miRNAs may serve as a non-invasive biomarker for the diagnosis of PTC and the postoperative monitoring of its progression and recurrence.