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Determination of the prognostic potential of hypoxia induced genes (HIF, GLUT1 and CAIX) in breast cancer patients

Grant number: 17/03558-3
Support type:Regular Research Grants
Duration: February 01, 2018 - January 31, 2019
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Beatriz da Costa Aguiar Alves Reis
Grantee:Beatriz da Costa Aguiar Alves Reis
Home Institution: Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil
Assoc. researchers:Auro del Giglio ; Fernando Luiz Affonso Fonseca

Abstract

The continued growth and progression of tumor cell requires a high bioenergetics expenditure. The more efficient cellular process to generate energy is glucose metabolism; despite adequate glucose uptake, not all cells have an adequate supply of oxygen available for their metabolism. Hypoxia is the term used to describe the deficiency of oxygen in some tissues. Tumor cells are particularly prone to hypoxia due to its high density and poor vascularization, which limits its oxygen supply. It is known that cells under hypoxic need a glucose uptake 19 times higher than those in normoxia, which causes overexpression of the protein glucose transporter (GLUT) and carbonic anhydrase (CAIX) - essential for eliminating the acids products of glycolysis and acidification of the tumor extracellular environment - in tumor cells. The expression of these two genes is influenced by factors induced by hypoxia (HIF-hypoxia-inducible factors), a highly conserved family of transcription factors activated by hypoxia that regulate the effects of cell oxygen sensor and a number genes encoding proteins of the glycolytic pathway. Clinically, HIF-1, CAIX and GLUT1 are associated with increased distant metastases and poor prognosis in a number of tumors. In this project, we propose to study the expression of these markers in peripheral blood sequential samples from patients with breast cancer undergoing chemotherapy treatment in order to determine its prognostic potential in liquid biopsies. (AU)