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Cellular Oncology
Published in: Cellular Oncology 5/2019

01-10-2019 | Breast Cancer | Original Paper

Clinical and biological impact of miR-18a expression in breast cancer after neoadjuvant chemotherapy

Authors: Ginés Luengo-Gil, Elena García-Martínez, Asunción Chaves-Benito, Pablo Conesa-Zamora, Esther Navarro-Manzano, Enrique González-Billalabeitia, Elisa García-Garre, Alberto Martínez-Carrasco, Vicente Vicente, Francisco Ayala de la Peña

Published in: Cellular Oncology | Issue 5/2019

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Abstract

Purpose

The analysis of breast cancer residual tumors after neoadjuvant chemotherapy (nCT) may be useful for identifying new biomarkers. MicroRNAs are known to be involved in oncogenic pathways and treatment resistance of breast cancer. Our aim was to determine the role of miR-18a, a member of the miR-17-92a cluster, in breast cancer behavior and outcome after nCT.

Methods

Pre- and post-nCT tumor miR-18a expression was retrospectively assessed by qRT-PCR in 121 patients treated with nCT and was correlated with survival outcomes and with clinical and pathological characteristics. Breast cancer-derived MCF-7 and MDA-MB-231 cell lines were transfected with miR-18a and anti-miR-18a to evaluate the biological effects of this molecule. In addition, whole-transcriptome expression analysis was performed.

Results

High miR-18a expression in post-nCT residual tumors was found to be associated with a significantly worse overall survival [hazard ratio (HR): 2.80, 95% confidence interval (CI): 1.01–7.76] and a strong trend towards a poorer disease-free survival (HR: 2.44, 95% CI: 0.99–5.02) compared to low miR-18a expressing post-nCT residual tumors. Clinical and experimental data were found to be in conformity with the proliferative effects of miR-18a, which showed a significant correlation with Ki67 and MYBL2 expression, both in pre- and post-nCT tumors and in public databases. In vitro analysis of the role of miR-18a in breast cancer-derived cell lines showed that a high expression of miR-18a was associated with a low expression of the estrogen receptor (ER), a decreased sensitivity to tamoxifen and an enrichment in luminal B and endocrine resistance gene expression signatures.

Conclusions

From our data we conclude that post-nCT miR-18a expression in breast cancer serves as a negative prognostic marker, especially in luminal tumors. Clinical, in vitro and in silico data support the role of miR-18a in breast cancer cell proliferation and endocrine resistance and suggest its potential utility as a biomarker for additional adjuvant treatment in patients without a pathologic complete response to neoadjuvant therapy.
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Metadata
Title
Clinical and biological impact of miR-18a expression in breast cancer after neoadjuvant chemotherapy
Authors
Ginés Luengo-Gil
Elena García-Martínez
Asunción Chaves-Benito
Pablo Conesa-Zamora
Esther Navarro-Manzano
Enrique González-Billalabeitia
Elisa García-Garre
Alberto Martínez-Carrasco
Vicente Vicente
Francisco Ayala de la Peña
Publication date
01-10-2019
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 5/2019
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-019-00450-2

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