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Diagnostic and prognostic markers useful in the clinical practice for patients with thyroid nodules: validation of previous findings and functional studies

Grant number: 15/20748-5
Support type:Regular Research Grants
Duration: March 01, 2016 - July 31, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Silvia Regina Rogatto
Grantee:Silvia Regina Rogatto
Home Institution: Faculdade de Medicina (FMB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Assoc. researchers:Fabio Albuquerque Marchi ; Luiz Paulo Kowalski

Abstract

Thyroid nodules are common in adult population, being detected in up to 70% of cases by ultrasound tests. However, current diagnostic methods have limitations in distinguishing malignant from benign follicular lesions, resulting in a significant number of potentially preventable surgeries. Thus, molecular diagnostic and prognostic tools useful in the clinical practice for thyroid lesions are of great interest. In two previous studies of our group, potential markers were identified based on the comprehensive analysis of gene expression and DNA methylation in malignant and benign thyroid lesions. Based on these preliminary results obtained in surgical specimens, the goal of this study is to prospectively test the potential of these putative diagnostic markers in thyroid lesions obtained directly from fine needle aspiration biopsies (FNAB). Due to the high frequency of BRAF mutations in cases of papillary thyroid carcinoma (PTC), the evaluation of this alteration will be incorporated to improve the performance of the test based on DNA analysis. In a second prior study of our group, DNA methylation profile of PTC paired with adjacent normal tissue samples revealed the involvement of differentially methylated miRNA-encoding genes. PTC is the most common thyroid malignancy, and despite the generally indolent tumor behavior, some of the patients have aggressive disease with no effective therapeutic options. Thus, we intend to perform a functional study addressing the impact of methylation and expression of these miRNAs in thyroid cancer cell lines. This project was designed with two main objectives: (1) to confirm the applicability and performance of the molecular assays using biopsies obtained at AC Camargo Cancer Center and (2) to characterize the epigenetic changes involved in the regulation of the miRNAs expression and to perform functional assays, which may allow advancing knowledge of PTC carcinogenesis with potential to reveal new therapeutic targets. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BARROS-FILHO, MATEUS CAMARGO; PEWARCHU, MICHELLE; MINATEL, BRENDA DE CARVALHO; SAGE, ADAM P.; MARSHALL, ERIN A.; MARTINEZ, VICTOR D.; ROCK, LEIGHA D.; MACAULAY, GAVIN; KOWALSKI, LUIZ PAULO; ROGATTO, SILVIA REGINA; GARNIS, CATHIE; LAM, WAN L. Previously undescribed thyroid-specific miRNA sequences in papillary thyroid carcinoma. JOURNAL OF HUMAN GENETICS, v. 64, n. 5, p. 505-508, MAY 2019. Web of Science Citations: 0.
BARROS-FILHO, MATEUS CAMARGO; MENEZES DE LIMA, LARISSA BARRETO; DOS REIS, MARIANA BISARRO; HOMEM DE MELLO, JULIA BETTE; BELTRAMI, CAROLINE MORAES; LOPES PINTO, CLOVIS ANTONIO; KOWALSKI, LUIZ PAULO; ROGATTO, SILVIA REGINA. PFKFB2 Promoter Hypomethylation as Recurrence Predictive Marker in Well-Differentiated Thyroid Carcinomas. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 20, n. 6 MAR 16 2019. Web of Science Citations: 0.
DIAS PAYAO ORTIZ, ISABELLA MARIA; BARROS-FILHO, MATEUS CAMARGO; DOS REIS, MARIANA BISARRO; BELTRAMI, CAROLINE MORAES; MARCHI, FABIO ALBUQUERQUE; KUASNE, HELLEN; DO CANTO, LUISA MATOS; HOMEM DE MELLO, JULIA BETTE; ABILDGAARD, CECILIE; LOPES PINTO, CLOVIS ANTONIO; KOWALSKI, LUIZ PAULO; ROGATTO, SILVIA REGINA. Loss of DNA methylation is related to increased expression of miR-21 and miR-146b in papillary thyroid carcinoma. CLINICAL EPIGENETICS, v. 10, NOV 20 2018. Web of Science Citations: 1.
DOS REIS, MARIANA BISARRO; BARROS-FILHO, MATEUS CAMARGO; MARCHI, FABIO ALBUQUERQUE; BELTRAMI, CAROLINE MORAES; KUASNE, HELLEN; LOPES PINTO, CLOVIS ANTONIO; AMBATIPUDI, SRIKANT; HERCEG, ZDENKO; KOWALSKI, LUIZ PAULO; ROGATTO, SILVIA REGINA. Prognostic Classifier Based on Genome-Wide DNA Methylation Profiling in Well-Differentiated Thyroid Tumors. JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, v. 102, n. 11, p. 4089-4099, NOV 1 2017. Web of Science Citations: 9.
BELTRAMI, CAROLINE MORAES; DOS REIS, MARIANA BISARRO; BARROS-FILHO, MATEUS CAMARGO; MARCHI, FABIO ALBUQUERQUE; KUASNE, HELLEN; LOPES PINTO, CLOVIS ANTONIO; AMBATIPUDI, SRIKANT; HERCEG, ZDENKO; KOWALSKI, LUIZ PAULO; ROGATTO, SILVIA REGINA. Integrated data analysis reveals potential drivers and pathways disrupted by DNA methylation in papillary thyroid carcinomas. CLINICAL EPIGENETICS, v. 9, MAY 2 2017. Web of Science Citations: 11.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.