Circular RNAs and thyroid cancer: Closed molecules, open possibilities.

Thyroid neoplasms requiring differential diagnosis between thyroid cancer and benign tumors can be detected in more than half of the healthy population. A generally accepted method that allows assessing the risk of malignant potential and determining the indications for surgical treatment of thyroid tumor is a fine-needle aspiration biopsy followed by a cytological examination. Nevertheless, in patients with indeterminate categories of cytological conclusions according to Bethesda system, the positive predictive value of the cytology result is significantly lower than desired and often leads to unjustified surgical treatment. In this regard, the search for alternative diagnostic solutions continues. Circular RNAs are a group of non-coding RNAs distinguished by a closed structure formed by covalent bonding of the nucleotide chain ends. Recent studies allow us to conclude that many different circular RNAs are involved in processes mediating oncogenesis in the thyroid gland, and their altered expression in tissue, blood, and exosomes of plasma may be a characteristic sign of thyroid cancer and certain clinicopathological features of its course. The purpose of this review is to analyze the accumulated data on the association of various circular RNAs with thyroid cancer and to discuss possible ways to improve the diagnosis and treatment of the disease based on the assessment of the expression of these molecules.

[The possibility of using freely circulating DNA blood plasma in preoperative diagnosis of thyroid tumors].

BACKGROUND: The feasibility of using molecular genetic markers for the diagnosis of thyroid tumors and the impact on the prognosis of thyroid cancer are being actively investigated. The most interesting are genes, the detection of which is associated not only with thyroid cancer, but also with a more aggressive course of the disease. The ability to diagnose the molecular profile of minimally invasive methods with the study of freely circulating DNA tumor tissue in blood plasma is a modern trend of medicine. AIMS: to evaluate the frequency of somatic mutations in the «hot spots» of BRAF, KRAS, KRAS, EIF1AX and TERT genes in circulating DNA of blood plasma. MATERIALS AND METHODS: Samples of DNA, extracted from the removed tumor and non-tumor thyroid tissue, were tested for the presence of somatic mutations in hot spots of the genes BRAF, KRAS, NRAS, TERT, and EIF1AX and then in identifying mutations and testing appropriate samples of free circulating DNA in blood plasma. RESULTS: mutations in the» hot spots «of the BRAF gene (exon 15, codon area 600-601) were found in 54 patients, mutations in the» hot spots « of the NRAS gene (exon 3, codon 61) – in 12 patients; mutations in the hot spots of the KRAS, TERT and EIF1AX genes were not detected. In freely circulating blood plasma DNA, BRAF gene mutations were detected in 1 case, NRAS gene mutations were detected in 1 case. CONCLUSIONS: the use of freely circulating DNA of blood plasma in the testing of the studied sample did not show the feasibility for the diagnosis of thyroid tumors.

[Oxidative stress and its role in the development of autoimmune thyroid diseases].

A large number of socially significant diseases is accompanied with oxidative stress and carry with tissue damage. Free radicals play a crucial role in the development of these diseases. Similar processes occur under the influence of ionizing radiation and bacterial infections. Recently, was indicated the significant role of oxidative stress in the development of autoimmune thyroiditis. It is assumed that the synthesis of thyroid hormones depends on the concentration of H2O2, which, due to its high toxicity, must be in strict accordance with the activity of antioxidant systems. Many biochemically negative processes occur on the apical membrane of the thyrocyte, which allows limiting the effect of free radicals and avoid cell destruction. However, in pathological conditions, enzymatic systems are disturbed and their components become abnormally activated in the cytoplasm, and it is leads to functional and morphological disorders. A deeper understanding of oxidative stress and its role in the development of autoimmune thyroiditis can contribute to the identification of new methods for its assessment, the expansion of therapeutic ranges for this disease. This review discusses oxidative stress, which is the accumulation of active damaging agents (free radicals, prooxidants, reactive oxygen species) that initiate cell damage and lead to the development of various pathological conditions.

[The role of molecular testing in thyroid tumors].

¹I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia; ²Endocrinology Research Centre, Moscow, Russia Thyroid cancer is the most common endocrine gland cancer. In the last few decades, the molecular diagnostics for thyroid tumors have been widely researched. It is one of the few cancers whose incidence has increased in recent years from microcarcinomas to common, large forms, in all age groups, from children to the elder people. Most researches focus on the genetic basis, since our current knowledge of the genetic background of various forms of thyroid cancer is far from being complete. Molecular and genetic research has several main directions: firstly, differential diagnosis of thyroid tumors, secondly, the prognostic value of detected mutations in thyroid cancer, and thirdly, targeted therapy for aggressive or radioactive iodine-resistant forms of thyroid cancer. In this review, we wanted to update our understanding and describe the prevailing advances in molecular genetics of thyroid cancer, focusing on the main genes associated with the pathology and their potential application in clinical practice.