miRNA profile obtained by next‑generation sequencing in metastatic breast cancer patients is able to predict the response to systemic treatments

Martinez‑Gutierrez,Antonio   Daniel; Catalan,Oliver   Millan; Vázquez‑Romo,Rafael; Porras Reyes,Fany   Iris; Alvarado‑Miranda,Alberto; Lara Medina,Fernando; Bargallo‑Rocha,Juan   E.; Orozco Moreno,Luz   Tonatzin; Cantú De León,David; Herrera,Luis   Alonso; López‑Camarillo,César; Pérez‑Plasencia,Carlos; Campos‑Parra,Alma   D.

doi:10.3892/ijmm.2019.4292

miRNA profile obtained by next‑generation sequencing in metastatic breast cancer patients is able to predict the response to systemic treatments

Authors:
- Antonio Daniel Martinez‑Gutierrez
- Oliver Millan Catalan
- Rafael Vázquez‑Romo
- Fany Iris Porras Reyes
- Alberto Alvarado‑Miranda
- Fernando Lara Medina
- Juan E. Bargallo‑Rocha
- Luz Tonatzin Orozco Moreno
- David Cantú De León
- Luis Alonso Herrera
- César López‑Camarillo
- Carlos Pérez‑Plasencia
- Alma D. Campos‑Parra
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Affiliations: Laboratorio de Genómica, Instituto Nacional de Cancerología (INCan), UNAM, Mexico City 14080, Mexico, Departamento de Cirugía de Tumores Mamarios, Instituto Nacional de Cancerología (INCan), UNAM, Mexico City 14080, Mexico, Servicio de Anatomía Patológica, Instituto Nacional de Cancerología (INCan), UNAM, Mexico City 14080, Mexico, Unidad de Cáncer de Mama, Instituto Nacional de Cancerología (INCan), UNAM, Mexico City 14080, Mexico, Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología (INCan)‑Instituto de Investigaciones Biomédicas, UNAM, Mexico City 14080, Mexico, Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México, CDMX, Mexico City 03100, Mexico
Published online on: July 30, 2019 https://doi.org/10.3892/ijmm.2019.4292
Pages: 1267-1280
Copyright: © Martinez‑Gutierrez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Metastatic breast cancer (MBC) is a challenge for oncologists, and public efforts should focus on identifying additional molecular markers and therapeutic management to improve clinical outcomes. Among all diagnosed cases of breast cancer (BC; approximately 10%) involve metastatic disease; notably, approximately 40% of patients with early‑stage BC develop metastasis within 5 years. The management of MBC consists of systemic therapy. Despite different treatment options, the 5‑year survival rate is <20%, which may be due to a lack of response with de novo or acquired resistance. MicroRNAs (miRNAs or miRs) are promising biomarkers as they are readily detectable and have a broad spectrum and potential clinical applications. The aim of this study was to identify a miRNA profile for distinguishing patients with MBC who respond to systemic treatment. Patients with MBC were treated according to the National Comprehensive Cancer Network guidelines. We performed miRNA‑Seq on 9 primary tumors using the Thermo Fisher Scientific Ion S5 system. To obtain global miRNA profiles, we carried out differentially expressed gene elimination strategy (DEGES) analysis between the responsive and non‑responsive patients. The results identified a profile of 12 miRNAs associated with the response to systemic treatment. The data were validated in an independent cohort (TCGA database). Based on the results, the upregulation of miR‑342‑3p and miR‑187‑3p was associated with the response to systemic treatment, and with an increased progression‑free survival (PFS) and overall survival (OS); by contrast, the downregulation of miR‑301a‑3p was associated with a higher PFS and OS. On the whole, the findings of this study indicate that these miRNAs may serve as biomarkers for the response to systemic treatment or the prognosis of patients with MBC. However, these data should be validated experimentally in other robust cohorts and using different specimens before implementing these miRNAs as biomarkers in clinical practice to benefit this group of patients.

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