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Open AccessArticle

Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients

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Department of Genetics, Federal University of Paraná, Curitiba 81531-980, Brazil
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Department of Cell and Molecular Biology, Federal University of Paraná, Curitiba 81531-980, Brazil
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Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba 81531-980, Brazil
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Carlos Chagas Institute - Fiocruz-Paraná, Curitiba 81350-010, Brazil
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Positivo University Medical School, Curitiba 81280-330, Brazil
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Nossa Senhora das Graças Hospital Breast Unit, Curitiba 80810-040, Brazil
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Department of Biomedical Data Sciences, Molecular Epidemiology, Leiden University Medical Center, 2300 R Leiden, The Netherlands
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Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20057, USA
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Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba 80230-020, Brazil
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Authors to whom correspondence should be addressed.
Biomolecules 2020, 10(1), 150; https://doi.org/10.3390/biom10010150
Received: 5 December 2019 / Revised: 10 January 2020 / Accepted: 15 January 2020 / Published: 16 January 2020
(This article belongs to the Special Issue microRNA Biomarkers in Clinical Study)
MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis as a screening strategy to identify EV-miRNAs derived from serum of clinically well-annotated breast cancer (BC) patients from the south of Brazil. EVs from three groups of samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated from serum using a precipitation method and analyzed by RNA-seq (screening phase). Subsequently, four EV-miRNAs (miR-142-5p, miR-150-5p, miR-320a, and miR-4433b-5p) were selected to be quantified by quantitative real-time PCR (RT-qPCR) in individual samples (test phase). A panel composed of miR-142-5p, miR-320a, and miR-4433b-5p distinguished BC patients from CT with an area under the curve (AUC) of 0.8387 (93.33% sensitivity, 68.75% specificity). The combination of miR-142-5p and miR-320a distinguished LA patients from CT with an AUC of 0.9410 (100% sensitivity, 93.80% specificity). Interestingly, decreased expression of miR-142-5p and miR-150-5p were significantly associated with more advanced tumor grades (grade III), while the decreased expression of miR-142-5p and miR-320a was associated with a larger tumor size. These results provide insights into the potential application of EVs-miRNAs from serum as novel specific markers for early diagnosis of BC. View Full-Text
Keywords: extracellular vesicles; circulating microRNAs; RNA-seq; miRNA; liquid biopsy extracellular vesicles; circulating microRNAs; RNA-seq; miRNA; liquid biopsy
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Ozawa, P.M.M.; Vieira, E.; Lemos, D.S.; Souza, I.L.M.; Zanata, S.M.; Pankievicz, V.C.; Tuleski, T.R.; Souza, E.M.; Wowk, P.F.; Urban, C.A.; Kuroda, F.; Lima, R.S.; Almeida, R.C.; Gradia, D.F.; Cavalli, I.J.; Cavalli, L.R.; Malheiros, D.; Ribeiro, E.M.S.F. Identification of miRNAs Enriched in Extracellular Vesicles Derived from Serum Samples of Breast Cancer Patients. Biomolecules 2020, 10, 150.

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