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Liquid biopsy as a non-invasive diagnostic and prognostic of thyroid tumors tool

Grant number: 20/06594-3
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): February 01, 2021
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Janete Maria Cerutti
Grantee:Débora Mota Dias Thomaz
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:14/06570-6 - Comprehensive whole exome, paired-end RNA and genome sequencing: new insights into genetic bases of thyroid carcinoma in pediatric and adult ages and applications in clinical practice, AP.TEM
Associated scholarship(s):23/03391-2 - A potential liquid biopsy biomarker: in vitro and in vivo study of the pathogenic role of NCOR1 on thyroid oncocytic carcinoma, BE.EP.DD


The prevalence of thyroid nodules has been increasing more and more in the last decades, and may occur in about 70% of adults when sensitive imaging methods, such as high-resolution ultrasound, are used. The diagnosis of thyroid nodules includes physical exams, clinical history and complementary methods such as ultrasound, fine needle aspiration (FNAB), analysis of thyroid function using imaging methods and laboratory tests. Although FNAB is the most accurate test to distinguish the malignant or benign nature of the nodules, in approximately 30% of the nodules it is not possible to identify malignancy criteria. In addition, this is an exam that is considered invasive. In order to overcome these limitations, several studies have sought to identify genetic and biochemical changes associated with the pathogenesis of Thyroid Cancer. Once these tumor-specific markers are identified, they can be tested in biological fluids. Liquid biopsy allows the detection, quantification and analysis of biomolecules from tumor cells, such as circulating cancer cells (CTCs), nucleic acids, proteins and vesicles in body fluids, such as blood. The nucleic acids, ctDNA (circulating tumor DNA) and ctRNA (circulating tumor RNA), are genetically representative of the tumor, containing all the genetic alterations that exist in the tumor genomic material, which can have a high diagnostic, prognostic and therapeutic value. This project aims to evaluate the use of liquid biopsy as a tool to help detect and quantify genetic changes for the purposes of diagnosis, prognosis and follow-up of patients with Thyroid Carcinoma. For this, we will select 150 patients (without evidence of disease and with evidence of disease) and 50 controls, whose material obtained from conventional biopsy has already been characterized by the group for mutations in the TERT, BRAF, RAS and AGK-BRAF, RET/PTC fusions and PAX8/PPARG that are being followed at the Thyroid Cancer outpatient clinic, Discipline of Endocrinology, Hospital São Paulo, EPM-Federal University of São Paulo. Blood from these patients will be obtained, from which free circulating DNA (cfDNA) and free circulating RNA (cfRNA) will be isolated to search, by digital PCR, for the genetic changes previously identified in each patient's primary tumor. For follow-up, serum thyroglobulin (sTg), anti-Tg antibody and TSH levels in the serum of these patients will be evaluated. The data obtained from the liquid biopsy will be correlated with the levels of sTg, as well as with clinical-pathological data to assess the accuracy of the test in the diagnosis, as well as, early detection of the persistence or recurrence of the disease in patients with Thyroid Cancer. (AU)

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