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

• Grant number: 19/05583-0
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: January 01, 2020
• End date: September 30, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Roger Chammas
• Grantee: Alexis Germán Murillo Carrasco
• Host 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)

Scientific publications

(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)

SOTOMAYOR, MARIANA BELEN VELASQUEZ; SEGURA, ANTHONY VLADIMIR CAMPOS; MONTALVA, RICARDO JOSE ASURZA; MARIN-SANCHEZ, OBERT; CARRASCO, ALEXIS GERMAN MURILLO; ROJAS, CESAR ALEXANDER ORTIZ. Establishment of a 7-gene expression panel to improve the prognosis classification of gastric cancer patients. FRONTIERS IN GENETICS, v. 14, p. 15-pg., 2023-09-12. (19/05583-0, 17/08430-5)

CARRASCO, ALEXIS GERMAN MURILLO; OTAKE, ANDREIA HANADA; MACEDO-DA-SILVA, JANAINA; SANTIAGO, VERONICA FEIJOLI; PALMISANO, GIUSEPPE; ANDRADE, LUCIANA NOGUEIRA DE SOUSA; CHAMMAS, ROGER. Deciphering the Functional Status of Breast Cancers through the Analysis of Their Extracellular Vesicles. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 24, n. 16, p. 33-pg., 2023-08-01. (18/15549-1, 18/18257-1, 20/04923-0, 21/00140-3, 19/05583-0)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

CARRASCO, Alexis Germán Murillo. Breast cancer-related heterogeneity reflected on circulating and vesicular miRNAs: high-throughput results and proof-of-concept for selecting tumor-derived extracellular vesicles. 2023. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina (FM/SBD) São Paulo.