1. Exosomal miRNA profile as complementary tool in the diagnostic and prediction of treatment response in localized breast cancer under neoadjuvant chemotherapy
- Author
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Francisco G. Ortega, Christian Rolfo, José Expósito, Diego de Miguel-Pérez, Jose L. Garcia-Puche, Alba Rodríguez-Martínez, Jordi Martorell-Marugán, María del Carmen Garrido-Navas, Marta Legueren, María José Serrano, José A. Lorente, Inmaculada Robles-Fernandez, Hugh Ilyine, Pedro Carmona-Sáez, [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, 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., and 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.
- Subjects
Oncology ,medicine.medical_treatment ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Evaluation Studies as Topic::Feasibility Studies [Medical Subject Headings] ,Exosomes ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Therapeutics::Combined Modality Therapy::Neoadjuvant Therapy [Medical Subject Headings] ,Anatomy::Body Regions::Breast [Medical Subject Headings] ,Exosomas ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings] ,Localized breast cancer ,0302 clinical medicine ,Circulating tumor cell ,Surgical oncology ,Positron Emission Tomography Computed Tomography ,Medicine ,Breast ,Prospective Studies ,Neoadjuvant therapy ,Anatomy::Cells::Neoplastic Cells, Circulating [Medical Subject Headings] ,microRNA ,Diagnóstico ,Conservative surgery ,Pronóstico ,MicroRNA ,Cancer diagnosis ,Middle Aged ,Progesterone Receptor Status ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Neoplastic Cells, Circulating ,Prognosis ,Metastatic breast cancer ,Neoadjuvant Therapy ,Treatment Outcome ,030220 oncology & carcinogenesis ,Neoplasias de la mama ,Female ,Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::Exosomes [Medical Subject Headings] ,Research Article ,medicine.medical_specialty ,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] ,Antineoplastic Agents ,Breast Neoplasms ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Gene Expression Profiling [Medical Subject Headings] ,lcsh:RC254-282 ,Neoadjuvant chemotherapy ,03 medical and health sciences ,Breast cancer ,Terapia neoadyuvante ,Internal medicine ,Biomarkers, Tumor ,Humans ,Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasms [Medical Subject Headings] ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis::Treatment Outcome [Medical Subject Headings] ,Chemotherapy ,Cancer prognosis ,business.industry ,Gene Expression Profiling ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents [Medical Subject Headings] ,Liquid Biopsy ,Circulating tumor cells ,Persons::Persons::Age Groups::Adult::Middle Aged [Medical Subject Headings] ,medicine.disease ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAs [Medical Subject Headings] ,MicroRNAs ,Check Tags::Female [Medical Subject Headings] ,Feasibility Studies ,Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Prognosis [Medical Subject Headings] ,business ,Células neoplásicas circulantes - 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., 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
- Published
- 2019