Avaliação do potencial de padrões de miRNAs como preditores de resposta patológica em pacientes com câncer de mama submetidos à terapia neoadjuvante

Abstract

Neoadjuvant therapy in breast cancer allows for the assessment of the degree of pathological response in the surgical specimen, providing prognostic and predictive information to guide subsequent treatments. Pathological complete response (PCR) is a prognostic factor widely associated with overall survival and is commonly used as a surrogate endpoint in neoadjuvant studies. Small non-coding RNAs, such as microRNAs (miRNAs), play crucial roles in various carcinogenic pathways and show promise as predictors of PCR. Developing a molecular signature of miRNAs extracted from tumor-derived extracellular vesicles (EVs) in peripheral blood holds potential for use as a biomarker. This approach could optimize neoadjuvant protocols to increase PCR rates and reduce toxicity. The present study aims to investigate the association between miRNAs derived from EVs and pathological complete response in patients with breast cancer undergoing neoadjuvant therapy. To this end, circulating EVs were isolated from peripheral blood samples collected before neoadjuvant treatment from 48 patients with breast cancer. Total RNAs contained in these vesicles were extracted using silica column-based methods and sequenced through next-generation sequencing (NGS). The miRNA expression patterns were correlated with PCR in surgical specimens through bioinformatics analysis, in order to obtain prognostic information. Among the 48 patients analyzed, a differential expression profile was noted in 12 patients with triple-negative breast cancer. Bioinformatics analysis revealed that overexpression of hsa-mir-489-5p was present in patients who achieved PCR, while overexpression of hsa-mir-1237-3p and hsa-mir-600-5p was observed in those without a complete pathological response. These findings suggest that hsa-mir-489-5p acts as a tumor suppressor, while hsa-mir-1237-3p and hsa-mir-600-5p function as oncomiRs, showing predictive potential for PCR. These miRNAs may represent a potential new tool for predicting response to neoadjuvant treatment, contributing to a more personalized and less invasive approach to breast cancer management.