Assessment of the risk of thyroid cancer recurrence using circulating microRNAs

Purpose of the study. To assess the prognostic significance of changes in the expression of microRNAs (miRNAs) in blood serum during the follow-up of patients with malignant tumors of the thyroid gland (thyroid) after radical surgery in order to identify tumors with high and low risk of recurrence.

Material and methods. The study included 138 patients with thyroid nodules identified by ultrasound examination and with an indeterminate cytological report based on fine-needle aspiration biopsy (FNA) (category III-V according to the Bethesda classification). All patients underwent surgical treatment with histological examination of surgical samples of thyroid tissue. Malignant thyroid masses were detected in 63 (45,7%) patients, and benign lesions in 75 (54,3%). Most patients had the initial stages of the malignancy T1-2N0M0 (n=44). The expression of miRNAs was assessed in fine needle aspiration material from the thyroid nodules and in blood serum using real-time PCR. The change in the expression of each miRNA in the substrate was assessed by determining the dCt relative to the reference miRNA-7a (Let-7a). The expression of miRNAs in blood serum was determined over time at 6, 12, 18 months after surgery, and parameters were compared depending on the presence or absence of the disease relapse.

Results. The most pronounced differences in miRNA expression between the samples of benign and malignant thyroid nodules, in the blood serum samples were noted for miRNA-146b, miRNA-222, miRNA-221. During two years of observation, cancer relapse was detected in 7 (11,1%) patients. When thyroid cancer relapsed 6 months after surgery, the expression of miRNA-146b and miRNA-221 increased, while in the absence of relapse it decreased compared to the preoperative level. At the same stage of observation, a unidirectional decrease in the expression of miRNA-222 in the blood serum was established in two subgroups, but the expression value of the marker during disease relapse was higher compared with the relapse-free patients (0,56 [0,25-0,73] versus 0,24 [0,13-0,36], p=0,048). A similar pattern of changes in miRNA expression in the blood was established 12 months after surgery.

Conclusion. Assessment of the expression of miRNA-146b, miRNA-221, and miRNA-222 in blood serum before surgery and 6 and 12 months after surgery has prognostic significance. With an increase in the postoperative level of expression of the studied miRNAs relative to the initial value, the risk of relapse is high, which justifies a subsequent increase in the frequency of postoperative patient examinations.

Key words: thyroid cancer, relapse, microRNA, expression, fine-needle aspiration biopsy, blood serum, molecular genetic study

Conflicts of interest. The authors have no conflicts of interest to declare.

Funding. There was no funding for this study