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    Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy

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    Author
    Rodríguez-Martínez, Alba
    de Miguel-Pérez, Diego
    Ortega, Francisco Gabriel
    Date
    2019
    Journal
    Breast Cancer Research
    Publisher
    BioMed Central Ltd.
    Type
    Article
    
    Metadata
    Show full item record
    See at
    https://dx.doi.org/10.1186/s13058-019-1109-0
    Abstract
    Background: Breast cancer patients under neoadjuvant chemotherapy includes a heterogeneous group of patients who eventually develop distal disease, not detectable by current methods. We propose the use of exosomal miRNAs and circulating tumor cells as diagnostic and predictive biomarkers in these patients. Methods: Fifty-three breast cancer women initially diagnosed with localized breast cancer under neoadjuvant chemotherapy were prospectively enrolled in this study. However, six of them were later re-evaluated and diagnosed as metastatic breast cancer patients by PET-CT scan. Additionally, eight healthy donors were included. Circulating tumor cells and serum exosomal miRNAs were isolated from blood samples before and at the middle of neoadjuvant therapy and exosomal miRNA levels analyzed by qPCR. Results: Before neoadjuvant therapy, exosomal miRNA-21 and 105 expression levels were higher in metastatic versus non-metastatic patients and healthy donors. Likewise, higher levels of miRNA-222 were observed in basal-like (p = 0.037) and in luminal B versus luminal A (p = 0.0145) tumor subtypes. Exosomal miRNA-222 levels correlated with clinical and pathological variables such as progesterone receptor status (p = 0.017) and Ki67 (p = 0.05). During neoadjuvant treatment, exosomal miRNA-21 expression levels directly correlated with tumor size (p = 0.039) and inversely with Ki67 expression (p = 0.031). Finally, higher levels of exosomal miRNA-21, miRNA-222, and miRNA-155 were significantly associated with the presence of circulating tumor cells. Conclusion: Liquid biopsies based on exosomal miRNAs and circulating tumor cells can be a complementary clinical tool for improving breast cancer diagnosis and prognosis. Copyright 2019 The Author(s).
    Sponsors
    This work was supported by "Granada Research of Excellence Initiative on BioHealth (GREIB)", the PhD grant from the University of Granada and the PhD grant from the Spanish Government (FPU) 2014, REF FPU14/05461.
    Keyword
    circulating tumor cells
    conservative surgery
    localized breast cancer
    neoadjuvant chemotherapy
    Cancer--Diagnosis
    Cancer--Prognosis
    Exosomes
    MicroRNAs
    Identifier to cite or link to this item
    https://www.scopus.com/inward/record.uri?eid=2-s2.0-85061121429&doi=10.1186%2fs13058-019-1109-0&partnerID=40&md5=7f4d87c6e2acf012560d3c82c23afbf8; http://hdl.handle.net/10713/8692
    ae974a485f413a2113503eed53cd6c53
    10.1186/s13058-019-1109-0
    Scopus Count
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    UMB Open Access Articles 2019

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