ANALYSIS OF RELATIVE EXPRESSION OF THE HMGA2 GENE AND ONCOGENIC MICRORNA-221 IN CYTOLOGICAL SLIDES OBTAINED BY A FINE-NEEDLE ASPIRATION BIOPSY OF THE THYROID NODULES

Abstract

Background. Fine-needle aspiration biopsy is recognized as the “gold standard” in the preoperative diagnosis of thyroid cancer. However, this method does not always allow reliable differentiation between benign and malignant thyroid nodules. Thus, the cytological report of a “follicular neoplasm or suspicious for a follicular neoplasm” suggests surgical lobectomy. However, in most cases, this conclusion does not point to follicular cancer but to benign neoplasm, follicular adenoma, where the surgical intervention is excessive. This implies the great relevance of finding biological markers capable of enhancing the specificity of detecting malignant neoplasms. Such markers may include an increase in the level of expression of oncogenes or a change in the expression of microRNA, since it is known that the content of a number of microRNAs changes significantly during the development of thyroid tumors.Materials and methods. The expression level of the HMGA2 gene, normally active at the embryonic stage, and oncogenic miRNA-221 microRNA was analyzed using real-time reverse transcription polymerase chain reaction in 713 cytological preparations of the thyroid gland (stained material dried on glasses) obtained by standard fine-needle aspiration biopsy. The sample included preparations corresponding to different cytological diagnoses: benign (n = 375), follicular neoplasm or suspicious for a follicular neoplasm (n = 143), medullary carcinoma (n = 7), papillary carcinoma (n = 186) and anaplastic carcinoma (n = 2).Results. The content of messenger RNA (mRNA) HMGA2 (P = 1.6 × 10–66, area under curve ROC 0.946) and miR-221 (P = 6.3 × 10–61, area under curve ROC 0.927) proved to be significantly elevated in papillary carcinoma compared to benign tumors. Follicular neoplasms showed significant heterogeneity in the quantity of both molecular markers. At the same time, an elevated level of miR-221 (3 times on average) was also characteristic of samples from this group with an increased level of expression of the HMGA2 gene (an average of 85 times). With regard to the quantity of these markers, the group of follicular neoplasms, in which no increase in the HMGA2 mRNA level was detected, did not differ from the group of benign nodules.Conclusions. The obtained results show that assessing the expression of HMGA2 mRNA and oncogenic miR-221 makes it possible to differentiate the papillary thyroid carcinoma from goiter at the preoperative stage, and based on the content of the HMGA2 mRNA, the group of follicular neoplasms can be divided into subgroups presumably differing in the risk of malignancy.

Keywords

• thyroid cancer
• molecular markers
• hmga2
• microrna-221
• fine needle aspiration biopsy