MicroRNAs validation as biomarkers for medullary thyroid carcinoma diagnosis

• Grant number: 19/16443-5
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: October 01, 2020
• End date: October 31, 2021
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Bruna Moretto Rodrigues
• Grantee: Bruna Moretto Rodrigues
• Company: Onkos Diagnósticos Moleculares Ltda. - ME
• CNAE: Atividades de serviços de complementação diagnóstica e terapêutica
• City: Ribeirão Preto
• Associated researchers: Ana Paula Carneiro dos Santos ; Andrei Félix de Oliveira ; Cléber Pinto Camacho ; Fabiano Mesquita Callegari ; Flávia Gaona de Oliveira Gennaro ; João Roberto Maciel Martins ; Marcos Tadeu dos Santos
• Associated scholarship(s): 20/13918-0 - microRNAs validation as biomarkers for Medullary Thyroid Carcinoma diagnosis, BP.TT

Abstract

The medullary thyroid carcinoma (MTC), although rarer than others differentiated thyroid carcinomas (around 3-4% cases), exhibits more aggressive behaviour, with mortality rate over 50% in late diagnosed cases and higher recurrence and metastasis risks even after total thyroidectomy surgery. It can be classified into two subtypes: sporadic (75% cases) and hereditary (25%), with sporadic subtype usually the worst prognosis, mainly due to its late diagnosis. MTC diagnosis usually comes though thyroid nodules identification by cervical imaging exams followed by fine-needle aspiration (FNA) biopsy. However, such exams diagnose under 50% cases on preoperative stage and despite existence of complementary exams such as calcitonin and CEA dosages, they are not performed routinely and have limitations that make their use controversial among researchers and doctors. In this context, the search for new diagnostic methodologies is crucial, and the necessity of an accurate, reliable and early diagnosis for MTC patients is visible. Molecular exams have proved to be a suitable tool for solving this problem. The use of microRNA-375 as MTC biomarker has been studied by several authors and although promising, its use is not well defined, since no author establishes or suggests a cut-off point that can be applied to the diagnosis. Preliminary data from Onkos suggest that miR-375 normalized expression may be an excellent early diagnostic parameter to MTC, however, a wider and focused study needs to be performed. Thus, the goal of the present project is to validate the miR-375 use as MTC biomarker, from definition of a threshold based on its expression, and assessed M918T and C634Y/R mutations in RET gene, to develop an early MTC diagnostic tool with high sensitivity and specificity. For this, 240 FNA smear slides samples collected after 2015 will be used, divided into three groups (MTC, benign and malignant non-MTC) for the analysis by qPCR. It is expected at the end of this project, the implementation and commercialization of a simple, accurate and robust molecular test to assist medicals decisions about MTC and benefit both patients and the healthcare system. Onkos excellence in molecular diagnostics area focused on thyroid resolutions, allied with the expertise of the researchers involved in the project, will contribute to the successful development of this product. (AU)