Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/3152
Title: Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
Authors: 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
metadata.dc.contributor.authoraffiliation: [Rodriguez-Martinez,A; de Miguel-Perez,D; Ortega,FG; Garcia-Puche,JL; Robles-Fernandez,I; Garrido-Navas,MC; Lorente,JA; Serrano,MJ] Liquid biopsy and metastasis research group, GENYO, Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government PTS, Granada, Spain. [Rodriguez-Martinez,A; de Miguel-Perez,D; Lorente,JA] Laboratory of Genetic Identification, Legal Medicine and Toxicology Department, Faculty of Medicine, University of Granada, Spain. [García-Puche,JL; Exposito,J; Legueren,M; Serrano,MJ] Comprehensive oncology division, Clinical University Hospital, Virgen de las Nieves-San Cecilio, Granada, Spain. [Martorell-Marugan,J; Carmona-Sáez,P] Bioinformatics Unit, GENYO, Centre for Genomics and Oncological Research: Pfizer/University of Granada/Andalusian Regional Government PTS. Granada, Spain. [Rolfo,C] Thoracic Medical Oncology, Early Clinical Trials, University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center (UMGCCC), Baltimore, USA. [Ilyine,H] DestiNA Genomics Ltd, Edinburgh, UK.
Keywords: Exosomes;MicroRNA;Circulating tumor cells;Localized breast cancer;Neoadjuvant chemotherapy;Conservative surgery;Cancer diagnosis;Cancer prognosis;Exosomas;Células neoplásicas circulantes;Neoplasias de la mama;Terapia neoadyuvante;Pronóstico;Diagnóstico
metadata.dc.subject.mesh: Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents
Medical Subject Headings::Anatomy::Body Regions::Breast
Medical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms
Medical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Feasibility Studies
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy
Medical Subject Headings::Anatomy::Cells::Neoplastic Cells, Circulating
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Prospective Studies
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome
Issue Date: 6-Feb-2019
Publisher: BioMed Central Ltd.
Citation: Rodríguez-Martínez A, de Miguel-Pérez D, Ortega FG, García-Puche JL, Robles-Fernández I, Exposito J, et al. Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy. Breast Cancer Res. 2019 Feb 6;21(1):21.
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.
URI: http://hdl.handle.net/10668/3152
metadata.dc.relation.publisherversion: https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-019-1109-0
metadata.dc.identifier.doi: 10.1186/s13058-019-1109-0
ISSN: 1465-5411 (Print)
1465-542X (Online)
Appears in Collections:01- Artículos - GENYO. Centro Pfizer-Andalucía de Genómica e Investigación Oncológica
01- Artículos - Hospital San Cecilio
01- Artículos - Hospital Virgen de las Nieves

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