VHL expression in case of thyroid tumor pathology: connection with the prevalence of the disease, expression of transcription, growth factors and components of the AKT / m-TOR signaling pathway

Introduction. The oncosuppressor protein VHL plays a decisive or at least important role in the mechanisms of tumor progression. The development of malignant neoplasms of the thyroid gland is associated with the activation of transcriptional and growth factors. However, the role of the VHL gene in the mechanisms of the development of thyroid cancer has hardly been studied. The study aimed to study the clinical and morphological features, expression of transcription, growth factors, and components of the AKT / m-TOR signaling pathway in patients with papillary thyroid cancer depending on the level of expression of the VHL gene. Material and methods. The study included 46 patients with tumor pathology of the thyroid gland: 20 patients with benign thyroid tumors and 26 patients with papillary thyroid cancer T1-4N0-2M0. The expression of parameters was determined by PCR in real-time. Mutation BRAF-V600E was determined in allele-specific PCR in real-time. Results and their discussion. The mRNA level of the VHL gene remained virtually unchanged in the tissue of papillary cancer and benign thyroid tumors. It depended on the prevalence of the disease, the defeat of regional lymph nodes, and the BRAF-V600E status. In the presence of the BRAF-V600E mutation, VHL expression increased 615 times in patients with a mutation compared with patients without this somatic mutation. It was revealed that the expression of NF-κB p65, NF-κB p50, HIF-1, HIF-2, growth factors VEGF and CAIX in patients in the group with a VHL level> 1.0 RU increased compared with patients with a VHL level <1.0 RU. A decrease in PDK, c-RAF, mTOR, 70s 6 kinase, PTEN mRNA levels were also recorded in patients with increased levels of VHL expression compared with patients with VHL expression <1.0 RU. Conclusion. That the association of the VHL expression with tumor progression in papillary thyroid cancer and the mutant protein bRAF presence was found. Also, associations between the VHL expression and the level of mRNA of transcription and growth factors are noted.

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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

Problems in oncology ◽

10.37469/0507-3758-2019-65-4-608-613 ◽

2019 ◽

Vol 65 (4) ◽

pp. 608-613

Author(s):

Lyudmila Spirina ◽

Svetlana Chizhevskaya ◽

Irina Kondakova ◽

Yevgeniy Choynzonov

Keyword(s):

Transcription Factors ◽

Thyroid Cancer ◽

Growth Factors ◽

Signaling Pathway ◽

Papillary Thyroid Cancer ◽

Braf V600e Mutation ◽

Braf V600e ◽

Papillary Thyroid ◽

Tor Signaling ◽

Relationship Of

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.

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Expression of transcription and growth factors and the AKT/m-TOR signaling pathway components in papillary thyroid cancer

Problems of Endocrinology ◽

10.14341/probl9310 ◽

2018 ◽

Vol 64 (4) ◽

pp. 208-215

Author(s):

Liudmila V. Spirina ◽

Sventlana Yu. Chizhevskaya ◽

Irina V. Kondakova

Keyword(s):

Transcription Factors ◽

Thyroid Cancer ◽

Growth Factors ◽

Signaling Pathway ◽

Papillary Thyroid Cancer ◽

Mrna Level ◽

Thyroid Tissue ◽

Papillary Thyroid ◽

Benign Lesions ◽

Tor Signaling

Background: The molecular mechanism of thyroid cancer development is associated with changes in expression of transcription factors and growth factors accompanied by modified level of the AKT/m-TOR components. Aims. The aim of study was to determine NF-κB p65, NF-κB p50, HIF-1α, HIF-2α, VEGF, CAIX, VEGFR2 expression and mRNA level of the AKT/m-TOR signaling pathway components in papillary thyroid cancer compared to those in benign lesions. Material and methods: Forty patients aged 33—66 years with T1-4N0-2M0 papillary thyroid cancer (7 males and 33 females) were enrolled in the study. The mean age was 52.0±2.6 years. The comparison group included patients with benign lesions of thyroid tissue (4 males and 18 females) aged 38—66 years (mean age, 53.0±4.4 years). Expression levels of NF-κB p65, NF-κB p50, HIF-1α, HIF-2α, VEGF, CAIX, VEGFR2, and the AKT/m-TOR signaling pathway components were determined by RT-PCR using specific primers. Results: Increased expression of transcription factors NF-κB and HIF-2α was found in papillary thyroid cancer. The levels of AKT and PTEN mRNA were elevated in transformed tissues. c-Raf expression was reduced 2.1-fold in cancer compared to that in thyroid tissues with benign lesions. Multiple positive correlations were revealed between transcription and growth factors and the AKT/m-TOR signaling pathway components in cancer. An association between PTEN expression and the NF-κB mRNA level was revealed, being a sign of deregulation in the signaling cascade in cancer tissues. Conclusions: Overexpression of NF-κB, HIF-2α, AKT, PTEN and reduction of c-Raf expression is typical of thyroid papillary cancer.

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A mouse model of BRAF V600E mutated papillary thyroid cancer imitating sporadic conditions

Endocrine Abstracts ◽

10.1530/endoabs.56.oc9.3 ◽

2018 ◽

Author(s):

Iva Jakubikova ◽

Elin Schoultz ◽

Ellen Johansson ◽

Shawn Liang ◽

Konrad Patyra ◽

...

Keyword(s):

Thyroid Cancer ◽

Mouse Model ◽

Papillary Thyroid Cancer ◽

Braf V600e ◽

Papillary Thyroid

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Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted papillary thyroid cancer aggressiveness

Oncotarget ◽

10.18632/oncotarget.13400 ◽

2016 ◽

Vol 8 (1) ◽

pp. 900-914 ◽

Cited By ~ 5

Author(s):

Tao Zhang ◽

Xiaopei Shen ◽

Rengyun Liu ◽

Guangwu Zhu ◽

Justin Bishop ◽

...

Keyword(s):

Thyroid Cancer ◽

Papillary Thyroid Cancer ◽

Braf V600e ◽

Papillary Thyroid ◽

Cancer Aggressiveness

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BRAF V600E Decreases Survival in Patients with Papillary Thyroid Cancer–Related Lymph Node Metastases

Clinical Thyroidology ◽

10.1089/ct.2021;33.403-405 ◽

2021 ◽

Vol 33 (9) ◽

pp. 403-405

Author(s):

Lilah F. Morris-Wiseman

Keyword(s):

Thyroid Cancer ◽

Lymph Node ◽

Papillary Thyroid Cancer ◽

Lymph Node Metastases ◽

Braf V600e ◽

Papillary Thyroid ◽

Node Metastases

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Correlation between F18-FDG PET/CT Imaging and BRAF V600E Genetic Mutation for the Early Assessment of Treatment Response in Papillary Thyroid Cancers

Journal of Personalized Medicine ◽

10.3390/jpm10020052 ◽

2020 ◽

Vol 10 (2) ◽

pp. 52

Author(s):

Andra Piciu ◽

Maria-Iulia Larg ◽

Doina Piciu

Keyword(s):

Thyroid Cancer ◽

Prognostic Factors ◽

Papillary Thyroid Cancer ◽

Genetic Mutation ◽

Braf V600e Mutation ◽

Braf V600e ◽

Papillary Thyroid ◽

Early Assessment ◽

Pet Ct ◽

Ct Evaluation

In thyroid neoplastic pathology, the BRAF V600E mutation is shown to be involved in the oncogenesis of papillary thyroid cancer and its subtypes. The purpose of this study is to evaluate the correlation between the mutation of the BRAF V600E oncogene and the pathological standardized uptake values (SUV) at the F18-fluorodeoxyglucose (F18-FDG) positron emission tomography/computed tomography (PET/CT) evaluation, for a group of 20 patients with radically treated (total thyroidectomy and radioiodine therapy) papillary thyroid cancer, with subclinical persistent disease, at 6 months after the initial treatment. We analyzed the correlations between the values of SUV and the presence of the BRAF mutation as well with other prognostic factors such as stage, age, specific tumor markers (thyroglobulin and anti-thyroglobulin), extrathyroid extension, the presence of metastatic lymph nodes or distant metastasis. The value of SUV in the case of BRAF+ (positive) patients was higher than in the negative ones, but without statistical significance, thus, the values of the SUV cannot be a predictable factor for the presence of the genetic mutation. There was a statistically significant correlation in BRAF+ subgroup between the SUV values and the positive resection limit following surgery, showing a higher SUV value in the PET/CT evaluation. No correlation was observed between the aforementioned prognostic factors involved in papillary thyroid cancer and the BRAF V600E mutation.

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