Anti-inflammatory activity and transport of microRNA by High-Density Lipoproteins (HDL) in Breast Câncer: association with the prognosis of the disease predicted by tumor molecular classification

• Grant number: 21/02401-9
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): August 01, 2021
• Effective date (End): May 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal researcher: Marisa Passarelli
• Grantee: Monique de Fatima Mello Santana
• Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The etiopathogenesis of breast cancer is diverse and the molecular classification of tumors and the calculation of the recurrence score are used as a basis for prognosis and therapeutic choice. High- density lipoproteins (HDL) are inversely associated with tumor genesis, as they modulate the lipid content, necessary for tumor replication, adhesion and migration, and perform antioxidant and anti-inflammatory functions. In addition, HDL carries microRNA (miR) that are capable of controlling the expression of different proteins and whose differential expression assumes great relevance in tumor genesis and progression. The objective of this project is to valuate in women newly diagnosed with breast cancer the concentration of miR in HDL and anti-inflammatory activity of these lipoproteins. Female subjects, between 18 and 80 years old (n = 200), with a recent diagnosis of breast cancer, treatment virgins and with the molecular classification and clinical prognostic stage of the tumor from I to III will be included. Healthy women in the same age group, matched for age and body mass index will be included as a control group (n = 200). HDL will be isolated from plasma by ultracentrifugation and used in incubations with macrophages stimulated with lipopolysaccharides to assess its ability to inhibit the secretion of inflammatory cytokines. The target mRNA of each miR will be determined and correlated with the differential expression profile associated with breast cancer. The analyzed parameters will be associated with the tumor prognosis, determined by its molecular classification. Results will be important to determine whether HDL-carried miR can be used to predict the evolution of breast cancer, in association with its molecular classification; in addition to providing information about the functionality of HDL which can modulate the evolution of the disease. (AU)