Buenos Aires
Breast Cancer
Symposium

BA-BCS 2024

September 3 – 6, 2024

IFIBYNE Auditorium, FCEN-UBA

 

Roger Chammas

Session 3: Detection and treatment of TNBC

Circulating miRNAs as biomarkers for early onset triple negative breast cancer patients

Alexis Murillo Carrasco1, Luciana Nogueira de Sousa Andrade1,Patrícia Pintor dos Reis2, Maria Ferreira Alves1, Miyuki Uno1, Roger Chammas3

1- Center for Translational Research in Oncology. Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil 2- Experimental Research Unit, Botucatu Medical School, São Paulo, Brazil 3- Comprehensive Center for Precision Oncology, Universidade de São Paulo, São Paulo, Brazil

Breast cancer (BC) is a highly heterogeneous disease. While immunohistochemical analysis has been instrumental in classifying patients into distinct subgroups, there remains a need to refine the molecular classification of the disease. In this study, we focused on circulating regulatory RNA molecules (microRNAs, miRNAs) present as cell-free sources (cf-miRNAs) in plasma, exploring their potential as biomarkers to distinguish between different BC subtypes and their onset (early vs. late). Additionally, we investigated miRNAs secreted by cells into extracellular vesicles (vesicular miRNAs, EV-miRNAs). Utilizing a high-throughput hybridization protocol (nCounter, Nanostring), we examined the complete cf-miRNA and EV-miRNA profiles in pooled samples from BC patients, categorized into major subtypes: Luminal A (n=3), Luminal B (n=6), Luminal HER2 (n=6), HER2+ (n=3), and Triple-Negative (TNBC, n=12). Both cf-miRNA and EV-miRNA proved to be informative in discerning miRNA expression differences among BC subtypes. Notably, hsa-miR-197-3p was able to differentiate TNBC patients (cf-miRNA/EV-miRNA). Among the EV-miRNAs, hsa-miR-511-5p, hsa-miR-1206, hsa-miR-198, hsa-miR-33a-5p, hsa-miR-484, hsa-miR-627-3p, and hsa-miR-630 were indicative of early-onset TNBC patients and were proposed for validation in an independent cohort using the cost-effective technique of quantitative Reverse Transcription PCR (qRT-PCR). In an additional cohort of early-onset TNBC patients (n=20), we observed consistent expression of five out of seven markers tested using TaqMan probes. Interestingly, EV-miRNAs hsa-miR-627-3p, hsa-miR-511-5p, and hsa-miR-630 exhibited higher expression levels than the exogenous control (spike-in cel-miR-39-3p). As a future direction of this study, we aim to evaluate the potential of these pre-selected EV-miRNAs in i) monitoring patient status according to their treatments and ii) distinguishing early-onset TNBC patients from other non-triple-negative BC patients.