EV derived miR-21 as a promising biomarker for early diagnosis and tumor activity in discrete BC subtypes: The Exobreast project

BackgroundEmerging evidence highlights the key role of microRNA (miR)-21 in cell-to-cell communication and tumorigenesis. Limited knowledge exists on the expression and clinical meaning of miR-21 in extracellular vesicles (EVs) of breast cancer (BC) patients. Thus, the aim of this study has been to assess EV-derived miR-21 expression in different BC subsets.MethodsOne hundred women were enrolled: 30 with early BC, 30 with metastatic BC on treatment progression, 30 cancer survivors on follow up and 10 healthy controls matched for age and BMI. EVs, isolated from serum samples, were characterized by nanoparticle tracking analyzer (NTA), scanning electron microscopy (SEM) and atomic force microscopy (AFM) to detect their concentration, size and structure. The miR-21 in EVs was evaluated by Real Time PCR. The expression of miR-21 was compared between groups by calculating the ΔΔCt statistic and the fold change, considering miR-16 as the housekeeping gene. The ΔΔCt was calculated using a linear mixed model approach with gene x group interaction as the parameter of interest, adjusting for age, BMI and menopausal status, and considering random intercept and random slope terms to account for individual variability.ResultsNo differences in EVs size and concentration among the four groups were detected. Considering the early BC group, the clinical stage at diagnosis and tumor subtype did not influence miR-21 expression. Higher expression of miR-21 has been found in metastatic versus healthy controls (p= 0.029 95% CI -1.549 to -0.079), mainly in HER2+ and hormone receptor positive patients (p 0.0005 and 0.036, respectively). In particular, in HER2+ miR-21 was significantly higher in patients with active BC (early and metastatic) (p 0.002 95% CI -1,707 to -0,376) compared to control group.ConclusionsWhile further investigations shall be requested, our data on serum EV suggest that miR-21 may become a promising biomarker for early diagnosis and tumor activity, mainly in HER2+ BC.Legal entity responsible for the studyClaudia Omarini.FundingMIUR Dipartimenti Eccellenti 2022.DisclosureAll authors have declared no conflicts of interest.