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Journal of Oncology
Volume 2019, Article ID 8393769, 11 pages
Research Article

Identification of Cell-Free Circulating MicroRNAs for the Detection of Early Breast Cancer and Molecular Subtyping

1Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil
2Department of Clinical Oncology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
3Department of Mastology and Breast Reconstruction, Barretos Cancer Hospital, Barretos, Brazil
4Tumor Biobank, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
5Department of Basic and Oral Biology, School of Dentistry of Ribeirão Preto, University of São Paulo, Brazil
6Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal
7ICVS/3B’s-PT Government Associate Laboratory, Braga/Guimarães, Portugal
8Barretos School of Health Sciences, FACISB, Barretos, São Paulo, Brazil

Correspondence should be addressed to Marcia M. C. Marques; moc.liamg@arievlismcmm

Received 14 February 2019; Revised 15 April 2019; Accepted 19 June 2019; Published 8 August 2019

Guest Editor: Chia-Jung Li

Copyright © 2019 Karen C. B. Souza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Early detection is crucial for achieving a reduction in breast cancer mortality. Analysis of circulating cell-free microRNAs present in the serum of cancer patients has emerged as a promising new noninvasive biomarker for early detection of tumors and for predicting their molecular classifications. The rationale for this study was to identify subtype-specific molecular profiles of cell-free microRNAs for early detection of breast cancer in serum. Fifty-four early-stage breast cancers with 27 age-matched controls were selected for circulating microRNAs evaluation in the serum. The 54 cases were molecularly classified (luminal A, luminal B, luminal B Her2 positive, Her-2, triple negative). NanoString platform was used for digital detection and quantitation of 800 tagged microRNA probes and comparing the overall differences in serum microRNA expression from breast cancer cases with controls. We identified the 42 most significant (P ≤ 0.05, 1.5-fold) differentially expressed circulating microRNAs in each molecular subtype for further study. Of these microRNAs, 19 were significantly differentially expressed in patients presenting with luminal A, eight in the luminal B, ten in luminal B HER 2 positive, and four in the HER2 enriched subtype. AUC is high with suitable sensitivity and specificity. For the triple negative subtype miR-25-3p had the best accuracy. Predictive analysis of the mRNA targets suggests they encode proteins involved in molecular pathways such as cell adhesion, migration, and proliferation. This study identified subtype-specific molecular profiles of cell-free microRNAs suitable for early detection of breast cancer selected by comparison to the microRNA profile in serum for female controls without apparent risk of breast cancer. This molecular profile should be validated using larger cohort studies to confirm the potential of these miRNA for future use as early detection biomarkers that could avoid unnecessary biopsy in patients with a suspicion of breast cancer.