Introduction: MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs that act as negative regulators of gene expression. The miRNA expression is impaired in many types of human cancer including thyroid cancer. The tissue profile of miRNAs has been shown to be useful for differentiating benign from malignant thyroid nodules, however attainment of tissue samples requires an invasive procedure while blood sampling is minimally invasive and easy to obtain. The aim of this study was to evaluate the circulating levels of a series of miRNAs in 46 patients with nodular goiter in order to identify those that might be useful in the differential diagnosis of thyroid nodules.
Methods: Thirteen miRNAs (miR-222, miR-221, miR-146a, miR-146b, miR-21, miR-155, miR-181a miR-181c, miR-7, miR-30d, miR-126, miR-374th, miR-let7g) were extracted from serum, reverse transcribed, subjected to real-time PCR and then analyzed by the ΔΔCt method. 10/13 miRNAs were evaluated post-surgically in a subset of patients undergone thyrodectomy.
Results: 41/46 patients performed fine-needle aspiration cytology of the dominant nodule (20 benign, three non-diagnostic, six indeterminate, four suspicious for malignancy and eight malignant) and 28/46 patients underwent total thyroidectomy (14 benign lesions and 14 papillary thyroid cancer (PTC)). MiR-21 and -222 were higher in patients with benign histology compared to malignant. On the contrary miR-374a was significantly higher in patients with suspicious or malignant cytology and with PTC compared to those with benign disease. After thyroidectomy, the majority of miRNAs decreased while a minority of miRNAs increased or remained unchanged. Moreover miR-7 was significantly lower in patients ablated with radioiodine compared to those treated only surgically.
Conclusions: Our data, although preliminary, suggest the utility of circulating miRNAs (miR-374a showing the best diagnostic accuracy) in the differential diagnosis of thyroid nodules and the lower expression of miR-7 in patients ablated suggests its potential use as a tumor marker.