BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study
As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using mo...
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2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| author | Bruna C. Bertol Juliana D. Massaro Guilherme Debortoli André L. P. Santos Jéssica N. G. de Araújo Tatiana M. V. Giorgenon Matheus Costa e Silva Nathalie L. de Figueiredo-Feitosa Cristhianna V. A. Collares Luiz Carlos C. de Freitas Edson G. Soares Luciano Neder Vivian N. Silbiger Rodrigo T. Calado Léa M. Z. Maciel Eduardo A. Donadi |
| author_facet | Bruna C. Bertol Juliana D. Massaro Guilherme Debortoli André L. P. Santos Jéssica N. G. de Araújo Tatiana M. V. Giorgenon Matheus Costa e Silva Nathalie L. de Figueiredo-Feitosa Cristhianna V. A. Collares Luiz Carlos C. de Freitas Edson G. Soares Luciano Neder Vivian N. Silbiger Rodrigo T. Calado Léa M. Z. Maciel Eduardo A. Donadi |
| author_sort | Bruna C. Bertol |
| collection | DOAJ |
| description | As BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAF<sup>V600E</sup> and <i>TERT</i> promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAF<sup>V600E</sup> (52.9%) and <i>TERT</i><sup>C228T</sup> (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The <i>TERT</i> rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the <i>BRAF, TERT,</i> and/or <i>HLA-G</i> genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAF<sup>V600E</sup> and <i>TERT</i><sup>C228T</sup>; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the <i>BRAF</i> and/or <i>HLA-G</i> genes may explain their increased expression in the tumor milieu. |
| first_indexed | 2024-03-11T00:24:40Z |
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| language | English |
| last_indexed | 2024-03-11T00:24:40Z |
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| spelling | doaj.art-ac1da19ffca74ac5b2dcdca1a390bd542023-11-18T23:05:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151245910.3390/ijms241512459BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association StudyBruna C. Bertol0Juliana D. Massaro1Guilherme Debortoli2André L. P. Santos3Jéssica N. G. de Araújo4Tatiana M. V. Giorgenon5Matheus Costa e Silva6Nathalie L. de Figueiredo-Feitosa7Cristhianna V. A. Collares8Luiz Carlos C. de Freitas9Edson G. Soares10Luciano Neder11Vivian N. Silbiger12Rodrigo T. Calado13Léa M. Z. Maciel14Eduardo A. Donadi15Postgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDivision of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDepartment of Anthropology, University of Toronto, Mississauga, ON L5L 1C6, CanadaDepartment of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDepartment of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal 59012-570, BrazilDivision of Endocrinology and Metabolism, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDivision of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDivision of Endocrinology and Metabolism, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDivision of Clinical Immunology, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDepartment of Ophthalmology, Otorhinolaryngology and Head and Neck Surgery, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDepartment of Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDepartment of Pathology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDepartment of Clinical Analysis and Toxicology, Federal University of Rio Grande do Norte, Natal 59012-570, BrazilDepartment of Medical Imaging, Hematology, and Clinical Oncology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilDivision of Endocrinology and Metabolism, Department of Medicine, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilPostgraduate Program of Basic and Applied Immunology, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto 14049-900, BrazilAs BRAF, TERT, HLA-G, and microRNAs have been individually associated with papillary thyroid carcinoma (PTC), we aimed to evaluate the individual and collaborative role of these markers in PTC in the same patient cohort. HLA-G and BRAF tumor expression was evaluated by immunohistochemistry. Using molecular methods, BRAF<sup>V600E</sup> and <i>TERT</i> promoter mutations were evaluated in thyroid fine needle aspirates. MicroRNA tumor profiling was investigated using massively parallel sequencing. We observed strong HLA-G (67.96%) while BRAF (62.43%) staining was observed in PTC specimens. BRAF overexpression was associated with poor response to therapy. The BRAF<sup>V600E</sup> (52.9%) and <i>TERT</i><sup>C228T</sup> (13%) mutations were associated with extrathyroidal extension, advanced-age, and advanced-stage cancer. The <i>TERT</i> rs2853669 CC+TC genotypes (38%) were overrepresented in metastatic tumors. Nine modulated microRNAs targeting the <i>BRAF, TERT,</i> and/or <i>HLA-G</i> genes were observed in PTC and involved with cancer-related signaling pathways. The markers were individually associated with PTC features, emphasizing the synergistic effect of BRAF<sup>V600E</sup> and <i>TERT</i><sup>C228T</sup>; however, their collaborative role on PTC outcome was not fully demonstrated. The differentially expressed miRNAs targeting the <i>BRAF</i> and/or <i>HLA-G</i> genes may explain their increased expression in the tumor milieu.https://www.mdpi.com/1422-0067/24/15/12459thyroid cancermicroRNAspolymorphismsbiomarkers |
| spellingShingle | Bruna C. Bertol Juliana D. Massaro Guilherme Debortoli André L. P. Santos Jéssica N. G. de Araújo Tatiana M. V. Giorgenon Matheus Costa e Silva Nathalie L. de Figueiredo-Feitosa Cristhianna V. A. Collares Luiz Carlos C. de Freitas Edson G. Soares Luciano Neder Vivian N. Silbiger Rodrigo T. Calado Léa M. Z. Maciel Eduardo A. Donadi BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study International Journal of Molecular Sciences thyroid cancer microRNAs polymorphisms biomarkers |
| title | BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study |
| title_full | BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study |
| title_fullStr | BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study |
| title_full_unstemmed | BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study |
| title_short | BRAF, TERT and HLA-G Status in the Papillary Thyroid Carcinoma: A Clinicopathological Association Study |
| title_sort | braf tert and hla g status in the papillary thyroid carcinoma a clinicopathological association study |
| topic | thyroid cancer microRNAs polymorphisms biomarkers |
| url | https://www.mdpi.com/1422-0067/24/15/12459 |
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