Evaluation of BACH1 and IRE1± Expression in Peripheral Blood of Breast Cancer Patients: Implications for Liquid Biopsy

• Grant number: 24/10049-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2025
• End date: December 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Beatriz da Costa Aguiar Alves Reis
• Grantee: Marina Paschoal Silva
• Host Institution: Centro Universitário FMABC (FMABC). Santo André , SP, Brazil

Abstract

In neoplasms, ROS act as signaling molecules contributing to tumorigenesis. The antioxidant response is mediated by the Keap1-NRF2-ARE complex, negatively regulated by the BACH1 gene. In breast cancer, elevated BACH1 expression is linked to increased recurrence, while its decrease reduces the risk of metastasis. BACH1 also influences IRE1±, crucial in endoplasmic reticulum (ER) homeostasis, associated with various neoplasms. Accumulation of misfolded proteins in the ER triggers the UPR, an important mechanism, exploited by tumor cells to promote proliferation, metastasis, and chemotherapy resistance. The interaction of UPR with genetic networks highlights its role in cancer. Liquid biopsy, less invasive, is an alternative to traditional biopsy, analyzing body fluids for biomarkers like circulating tumor DNA and RNA. However, several studies have shown that analyzing genetic signatures obtained in whole blood (not just plasma) is a valuable tool for assessing diseases and drug resistance. The expression profile of BACH1 and IRE1± in breast cancer patients' peripheral blood has not yet been fully explored as a diagnostic and/or prognostic marker. The aim of this study will be to evaluate the expression of BACH1 and IRE1± in serial samples (at diagnosis and 3 and 6 months after the start of chemotherapy) of peripheral blood from breast cancer patients and healthy women and to associate this expression profile with clinical variables. Gene expression will be assessed by real-time PCR (qPCR).