Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes

Abstract Emerging evidence highlights the key role of microRNA (miR)-21 in cell-to-cell communication and tumorigenesis. However, limited knowledge exists on the levels and clinical meaning of miR-21 in extracellular vesicles (EVs) of patients with breast cancer (BC). We assessed EV-derived miR-21 l...

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Main Authors: Claudia Omarini, Virginia Catani, Ilenia Mastrolia, Angela Toss, Federico Banchelli, Chrystel Isca, Daniele Medici, Ornella Ponzoni, Marco Brucale, Francesco Valle, Maria Cristina Baschieri, Roberto D’Amico, Valentina Masciale, Chiara Chiavelli, Federica Caggia, Carlo Augusto Bortolotti, Federico Piacentini, Massimo Dominici
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Biomarker Research
Online Access:https://doi.org/10.1186/s40364-025-00724-y
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author Claudia Omarini
Virginia Catani
Ilenia Mastrolia
Angela Toss
Federico Banchelli
Chrystel Isca
Daniele Medici
Ornella Ponzoni
Marco Brucale
Francesco Valle
Maria Cristina Baschieri
Roberto D’Amico
Valentina Masciale
Chiara Chiavelli
Federica Caggia
Carlo Augusto Bortolotti
Federico Piacentini
Massimo Dominici
author_facet Claudia Omarini
Virginia Catani
Ilenia Mastrolia
Angela Toss
Federico Banchelli
Chrystel Isca
Daniele Medici
Ornella Ponzoni
Marco Brucale
Francesco Valle
Maria Cristina Baschieri
Roberto D’Amico
Valentina Masciale
Chiara Chiavelli
Federica Caggia
Carlo Augusto Bortolotti
Federico Piacentini
Massimo Dominici
author_sort Claudia Omarini
collection DOAJ
description Abstract Emerging evidence highlights the key role of microRNA (miR)-21 in cell-to-cell communication and tumorigenesis. However, limited knowledge exists on the levels and clinical meaning of miR-21 in extracellular vesicles (EVs) of patients with breast cancer (BC). We assessed EV-derived miR-21 levels in one hundred women: 30 with early BC (EBC), 30 with metastatic BC on treatment progression (MBC), 30 cancer survivors on follow-up (FU) and 10 healthy donors (HD) as age- and body mass index (BMI)-matched controls. EVs isolated from serum samples were characterized using nanoparticle tracking analysis, scanning electron microscopy and atomic force microscopy to detect their concentration, size, morphology and mechanical properties. The levels of miR-21 in EVs was evaluated using real time PCR and compared between groups (EBC, MBC and FU vs. HD) by calculating the fold change and ΔΔCt statistic. EVs size and concentration did not differ significantly among patient groups. In the EBC group, the clinical stage at diagnosis and tumor subtype did not influence miR-21 levels. The levels of miR-21 were higher in the MBC group than in the HD group (p = 0.029), mainly in those who were human epidermal growth factor receptor 2 (HER2)+ (p = 0.0005) and hormone receptor-positive (p = 0.036). In particular, in the HER2 + subgroup, the miR-21 levels were significantly higher in those with active BC (both EBC and MBC) than in HDs (p = 0.002). Our findings suggest that miR-21 may be a promising biomarker for diagnosis and tumor activity, mainly in HER2 + BC.
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spelling doaj-art-28132765f8f2436f9527f283a746d3d82025-01-26T12:45:37ZengBMCBiomarker Research2050-77712025-01-011311410.1186/s40364-025-00724-yExtracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypesClaudia Omarini0Virginia Catani1Ilenia Mastrolia2Angela Toss3Federico Banchelli4Chrystel Isca5Daniele Medici6Ornella Ponzoni7Marco Brucale8Francesco Valle9Maria Cristina Baschieri10Roberto D’Amico11Valentina Masciale12Chiara Chiavelli13Federica Caggia14Carlo Augusto Bortolotti15Federico Piacentini16Massimo Dominici17Division of Medical Oncology, Department of Oncology and Hematology, University Hospital of ModenaLaboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaLaboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaDivision of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaUnit of statistical and methodological support to clinical research, University Hospital of ModenaDivision of Medical Oncology, Sant’Antonio Abate Hospital of TrapaniLaboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaDivision of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaConsiglio Nazionale delle ricerche (CNR), Istituto per lo studio dei materiali nanostrutturati (ISMN)Consiglio Nazionale delle ricerche (CNR), Istituto per lo studio dei materiali nanostrutturati (ISMN)Division of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaUnit of statistical and methodological support to clinical research, University Hospital of ModenaLaboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaLaboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaDepartment of training, research and innovation, University Hospital of ModenaDepartment of Life Sciences, University of Modena and Reggio EmiliaDivision of Medical Oncology, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaLaboratory of Cellular Therapy, Department of Medical and Surgical Sciences for Children and Adults, University Hospital of ModenaAbstract Emerging evidence highlights the key role of microRNA (miR)-21 in cell-to-cell communication and tumorigenesis. However, limited knowledge exists on the levels and clinical meaning of miR-21 in extracellular vesicles (EVs) of patients with breast cancer (BC). We assessed EV-derived miR-21 levels in one hundred women: 30 with early BC (EBC), 30 with metastatic BC on treatment progression (MBC), 30 cancer survivors on follow-up (FU) and 10 healthy donors (HD) as age- and body mass index (BMI)-matched controls. EVs isolated from serum samples were characterized using nanoparticle tracking analysis, scanning electron microscopy and atomic force microscopy to detect their concentration, size, morphology and mechanical properties. The levels of miR-21 in EVs was evaluated using real time PCR and compared between groups (EBC, MBC and FU vs. HD) by calculating the fold change and ΔΔCt statistic. EVs size and concentration did not differ significantly among patient groups. In the EBC group, the clinical stage at diagnosis and tumor subtype did not influence miR-21 levels. The levels of miR-21 were higher in the MBC group than in the HD group (p = 0.029), mainly in those who were human epidermal growth factor receptor 2 (HER2)+ (p = 0.0005) and hormone receptor-positive (p = 0.036). In particular, in the HER2 + subgroup, the miR-21 levels were significantly higher in those with active BC (both EBC and MBC) than in HDs (p = 0.002). Our findings suggest that miR-21 may be a promising biomarker for diagnosis and tumor activity, mainly in HER2 + BC.https://doi.org/10.1186/s40364-025-00724-y
spellingShingle Claudia Omarini
Virginia Catani
Ilenia Mastrolia
Angela Toss
Federico Banchelli
Chrystel Isca
Daniele Medici
Ornella Ponzoni
Marco Brucale
Francesco Valle
Maria Cristina Baschieri
Roberto D’Amico
Valentina Masciale
Chiara Chiavelli
Federica Caggia
Carlo Augusto Bortolotti
Federico Piacentini
Massimo Dominici
Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
Biomarker Research
title Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
title_full Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
title_fullStr Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
title_full_unstemmed Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
title_short Extracellular vesicles-derived miR-21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
title_sort extracellular vesicles derived mir 21 as a biomarker for early diagnosis and tumor activity in breast cancer subtypes
url https://doi.org/10.1186/s40364-025-00724-y
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