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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

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 pa...

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Autores principales: Rodríguez-Martínez, Alba, de Miguel-Pérez, Diego, Ortega, Francisco Gabriel, García-Puche, José Luis, Robles-Fernández, Inmaculada, Exposito, José, Martorell-Marugan, Jordi, Carmona-Sáez, Pedro, Garrido-Navas, María del Carmen, Rolfo, Christian, Ilyine, Hugh, Lorente, José Antonio, Legueren, Marta, Serrano, María José
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366103/
https://www.ncbi.nlm.nih.gov/pubmed/30728048
http://dx.doi.org/10.1186/s13058-019-1109-0
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author Rodríguez-Martínez, Alba
de Miguel-Pérez, Diego
Ortega, Francisco Gabriel
García-Puche, José Luis
Robles-Fernández, Inmaculada
Exposito, José
Martorell-Marugan, Jordi
Carmona-Sáez, Pedro
Garrido-Navas, María del Carmen
Rolfo, Christian
Ilyine, Hugh
Lorente, José Antonio
Legueren, Marta
Serrano, María José
author_facet Rodríguez-Martínez, Alba
de Miguel-Pérez, Diego
Ortega, Francisco Gabriel
García-Puche, José Luis
Robles-Fernández, Inmaculada
Exposito, José
Martorell-Marugan, Jordi
Carmona-Sáez, Pedro
Garrido-Navas, María del Carmen
Rolfo, Christian
Ilyine, Hugh
Lorente, José Antonio
Legueren, Marta
Serrano, María José
author_sort Rodríguez-Martínez, Alba
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-019-1109-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-63661032019-02-15 Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy Rodríguez-Martínez, Alba de Miguel-Pérez, Diego Ortega, Francisco Gabriel García-Puche, José Luis Robles-Fernández, Inmaculada Exposito, José Martorell-Marugan, Jordi Carmona-Sáez, Pedro Garrido-Navas, María del Carmen Rolfo, Christian Ilyine, Hugh Lorente, José Antonio Legueren, Marta Serrano, María José Breast Cancer Res Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13058-019-1109-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-02-06 2019 /pmc/articles/PMC6366103/ /pubmed/30728048 http://dx.doi.org/10.1186/s13058-019-1109-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Rodríguez-Martínez, Alba
de Miguel-Pérez, Diego
Ortega, Francisco Gabriel
García-Puche, José Luis
Robles-Fernández, Inmaculada
Exposito, José
Martorell-Marugan, Jordi
Carmona-Sáez, Pedro
Garrido-Navas, María del Carmen
Rolfo, Christian
Ilyine, Hugh
Lorente, José Antonio
Legueren, Marta
Serrano, María José
Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
title Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
title_full Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
title_fullStr Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
title_full_unstemmed Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
title_short Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
title_sort exosomal mirna profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6366103/
https://www.ncbi.nlm.nih.gov/pubmed/30728048
http://dx.doi.org/10.1186/s13058-019-1109-0
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