GENE EXPRESSION OF INTEGRIN RECEPTORS AND THEIR LIGANDS IN PAPILLARY THYROID CARCINOMA WITH DIFFERENT BRAF V600E MUTATION STATUS

L.A. Mostovich(1), G.P. Logacheva(2), S.V. Svyatchenko(2), S.P. Shevchenko(3), L.F. Gulyaeva(1, 2)
1-Institute of Molecular Biology and Biophysics, Timakova str., 2, Novosibirsk, Russian Federation, 630117;
2-Novosibirsk National Research State University, Pirogova str., 2, Novosibirsk, Russian Federation, 630090;
3-Novosibirsk Municipal Clinical Hospital №1, Zaleskogo str., 6, Novosibirsk, Russian Federation, 630047;
E-mail: mostovichl@gmail.com

Introduction. Papillary thyroid cancer (PTC) is the most common malignancy of the endocrine system. As the most frequent genetic alteration BRAF V600E mutation in PTC leads to changes in the activity of intracellular signaling pathways. As a result, expression levels of cell membrane integrin receptors and their ligands-extracellular matrix proteins are modified. Such changes promote migration, invasion and metastasis of tumor cells. The aim of the study was to evaluate the gene expression profile of integrins ITGA3, ITGAV, ITGA6, ITGA9, ITGB1 and their ligands OPNa, OPNb, TSP1 in papillary carcinomas with different BRAF V600E mutation status. Methods. To evaluate expression levels of investigated genes intraoperative tissue samples of the thyroid gland from 41 PTC patients (n=26), diffuse nodular nontoxic goiter (n=10) and follicular adenoma (n=5) were investigated by real time RT-PCR, the presence of mutation was determined with the use of allele-specific amplification.Results. An increase of the gene expression level of ITGA3, ITGAV, ITGB1, OPNb and TSP1 was identified in PTC tissue, and the gene expression level of OPNb and TSP1 in tissue samples of regional metastases was found to be over than in compared conventionally normal tissue. In samples with a widespread process (T3, T4), expression levels of ITGA3, ITGA6 and ITGA9 were higher if compared to samples T1. Expression levels of ITGA 3and ITGAV in PTC samples BRAF V600E+ were over BRAF V600E- samples. Conclusion. Integrins and their ligands OPN and TSP1 can be considered as potential markers in the determination of the prognosis of PTC.
Keywords: 
papillary thyroid cancer, BRAF V600E mutation, integrins, osteopontin, thrombospondin-1