Document Type : Research Articles
Authors
1
Laboratory of Tumor Biochemistry, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Medical Sciences, Russian Federation.
2
Division of Biochemistry and Molecular, Russian Federation.
3
Division of Head and Neck Cancers, Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Medical Sciences, Russian Federation.
4
Division of Oncology, Siberian State Medical University, Russian Federation.
5
Siberian State Medical University, Tomsk, Russian Federation.
6
Cancer Research Institute, Siberian State Medical University, Tomsk, Russian Federation.
7
Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russian Federation.
Abstract
Objective: The aim of this study was investigation the AKT / mTOR signaling pathway components, transcriptional and growth factors, as well as steroid hormone receptors and nuclear factors Brn-3α and TRIM16 expression in the tissue of the primary thyroid tumor and metastases, depending on the BRAF- V600E status. Material and Methods: The study was enrolled 20 patients with PTCs, who underwent surgical treatment. They were divided into negative BRAF-V600E status (12 people), positive BRAF-V600E status (8 patients). Mutation status was assessed in paired metastatic tissue samples. The molecular marker expression was determined by real-time PCR. The Real-time-PCR-BRAF-V600E reagent kit evaluated the BRAF-V600E mutation. Results: A decrease in the PDK kinase, PTEN, VHL mRNA level in primary cancers was noted, compared with metastases’ tissue. An increase in AKT, GSK-3β, mTOR, 70s 6 kinase was revealed in cancers with point mutation compared with the primary tumor without a mutation. Positive mutation status was accompanied by an increase in NF-κB p65, NF-κBp50, VEGF HIF-2 VHL level compared to the primary tumor with negative BRAF-V600E status. In the metastases with the BRAF-V600E point mutation, a decrease in the PDK kinase, HIF-1; VHL; TRIM16, and ERα expression was observed, compared to lymph node metastases (LNMs) without the mutation. The concordance in the BRAF-V600E tumor status and LNMs was observed only in 50% of patients. If the BRAF gene status did not match PTCs and LNMs, an increase in the mTOR, NFkBp65, VHL, and ERα mRNA levels was found in the PTCs. In LNMs, there was an increase in the c-RAF PTEN NFkBp65 VHL expression compared to non-concordant ones. Conclusion: The heterogeneity in the primary tissue’s expression profile and metastases was noted. The BRAF-V600E mutation can affect the molecular characteristics both in the primary cancers and metastases. The discrepancy between the mutant status and the molecular factors expression variability in the primary tumor and LNMs determines its progression.
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