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Enrichment of STn/Tn+ tumor-derived extracellular microvesicles for evaluating miRNA-based biomarkers in Breast Cancer patients

Grant number: 19/05583-0
Support type:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): January 01, 2020
Effective date (End): September 30, 2022
Field of knowledge:Biological Sciences - Biochemistry - Molecular Biology
Principal researcher:Roger Chammas
Grantee:Alexis Germán Murillo Carrasco
Home Institution: Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira (ICESP). Coordenadoria de Serviços de Saúde (CSS). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Liquid biopsies arise as new diagnostic strategies in Cancer, aiming at the analysis of cell-free (cf) analytes in a less-invasive way than solid biopsies. As of today, a great controversy in the literature exists regarding the choice of the better liquid-biopsy target (cfDNA, cfRNA, cf-miRNA or extracellular-vesicles). Here we will focus on extracellular microvesicles (EMV) because they are cell fractions carrying and protecting RNA, miRNA, and DNA molecules. These vesicles are released in the blood, and act as agents for intercellular communication in Cancers (e.g., Breast, lung, prostate and bladder carcinomas); they are released not only by Cancer cells, but also by non-tumor cells and non-human cells (microbiota), and play a role in the host response to Cancer treatment. In particular, we will study tumor-derived extracellular microvesicles. The capture of these vesicles represents a technical challenge, due to their size (40-150 nm). We will take advantage of specific and aberrant glycosylation patterns found on tumor cells, and therefore on their EMV surface (such as derivatives of Tn antigen) for analyte enrichment. For that, we propose to use these affinity agents, such as lectins or antibodies. So, we intend to generate an early-diagnosis test for Breast Cancer (BC) through specific selection and enrichment of tumor-derived EMV; and further the analysis of these vesicles regarding the quantity and quality of the miRNA cargo of these EMV in the plasma of Breast Cancer patients. We will compare EMV levels for the four major subtypes of Breast Cancer and also test the expression of a miRNA panel among young and elderly patients with Triple-Negative Breast Cancer (TNBC). These findings will be evaluated as prognostic markers of Breast Cancer patients. (AU)

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