Combination of serum microRNAs and ultrasound profile as predictive biomarkers of diagnosis and prognosis for papillary thyroid microcarcinoma.

Circulating microRNAs (miRNAs) are promising diagnostic markers in various types of cancers, including papillary thyroid carcinoma (PTC). However, there is sparse information reported with regards to miRNA expression in papillary thyroid microcarcinoma (PTMC) or concerning the role of a combination of miRNAs and ultrasound (US) in the diagnosis of PTMC before surgery. Therefore, we designed a study that aimed to evaluate miRNA expression levels and their potential associations with US findings and determine whether miRNAs could be used as diagnostic and prognostic biomarkers of PTMC. miR‑222, miR‑221, miR‑146b and miR‑21 levels were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) in serum from 58 patients with PTMC and 47 with PTC, 35 patients with benign thyroid nodules (BTN) and 40 control subjects. Expression levels of the four miRNAs in serum were evaluated before and after surgery. The results indicated that miR‑222, miR‑221, miR‑146b and miR‑21 expression levels were higher in the PTMC samples than in those from the BTN and control groups and the combination of miRNAs and US had a high sensitivity and specificity for discrimination between BTN and PTMC by receiver operating characteristic (ROC) curve analysis and improved the accuracy of diagnosis of PTMC before surgery. In addition, serum miRNA expression levels were significantly related to poor prognostic factors including metastatic lymph nodules (MLNs), multifocal and bilateral lesions, advanced stage and high‑risk PTMC patients. The miRNA expression levels in serum from PTMC patients were rapidly reduced after surgery compared with levels before surgery. In addition, we also analyzed the miRNA expression levels in serum from patients who were divided into two groups according to factors indicating a good or poor prognosis associated with PTMC after surgery. The results suggested that after surgery, the miR‑222, miR‑146b and miR‑21 expression levels were significantly higher in the poor prognosis group compared with these levels in the good prognosis group. Serum miRNA expression levels helped distinguish between benign and malignant nodules and were associated with a poor prognosis in PTMC. Circulating miRNAs may be useful as follow‑up biomarkers and as diagnostic and prognostic tools.