The Relationship of the Braf-V600e Mutation With the Expression of Transcriptional, Growth Factors, Components of the Akt / M-Tor Signaling Pathway in the Tissue of Papillary Thyroid Cancer

Abstract

One of the initiating mutations in the development of thyroid cancer is BRAF-V600E, which leads to the various signaling cascades activation and changes in the production of transcription and growth factors. It is known that papillary thyroid cancer is characterized by activation of the expression of transcription factors NF-kB and HIF-2a and AKT/m-TOR signaling cascade. However, the relationship of the studied molecular markers in patients with the wild and mutant BRAF gene has not yet been studied. The aim of the work was to study the expression of transcription factors NF-65B p65 and NF-kB p50, HIF-1a, HIF-2a, growth factors VEGF, CAIX and VEGFR2, components of the AKT/m-TOR signaling pathway in patients with thyroid papillary cancer depending on the presence of mutations BRAF-V600E. Material and methods. It was included 40 patients with papillary thyroid cancer with the stage of the tumor process T1-4N0-2M0. The expression of the indicators was determined by real-time PCR. BRAF-V600E mutation was revealed by allele-specific PCR in real-time. Results and discussion. It was found that patients with the absence and presence of the BRAF-V600E mutation had similar clinical and morphological parameters of the disease, which was accompanied by a change in the molecular-biological characteristics of the tumor. The presence of the mutant form of the gene in the tumor led to a decrease in the AKT, cRAF, GSK-3P kinases mRNA levels and the overexpression of NF-kB p65, HIF-1 and VEGF. Conclusion. Patients with papillary thyroid cancer have no differences in the clinical and morphological characteristics of the disease, depending on the status of the BRAF-V600E gene, is characteristic. It was identified biological parameters associated with this somatic mutation. An increase in the mRNA level of growth and transcription factors was observed with a decrease in the activity of the AKT / m-TOR signaling pathway.