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Open Access Highly Accessed Research article

Oncogenic MicroRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum

Marek Sochor1, Petra Basova2, Michal Pesta3, Nina Dusilkova2, Jiri Bartos1, Pavel Burda2, Vit Pospisil2 and Tomas Stopka2*

Author Affiliations

1 Comprehensive Cancer Centre, Regional Hospital Liberec, Liberec, Czech Republic

2 1st Faculty of Medicine, Institute of Pathological Physiology, Charles University in Prague, Prague, Czech Republic

3 Faculty of Mathematics and Physics, Charles University in Prague, Prague, Czech Republic

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BMC Cancer 2014, 14:448  doi:10.1186/1471-2407-14-448

Published: 18 June 2014

Abstract

Background

MicroRNAs (miRs) represent a distinct class of posttranscriptional modulators of gene expression with remarkable stability in sera. Several miRs are oncogenic (oncomiRs) and are deregulated in the pathogenesis of breast cancer and function to inhibit tumor suppressors. Routine blood monitoring of these circulating tumor-derived products could be of significant benefit to the diagnosis and relapse detection of early-stage breast cancer (EBC) patients.

Methods

Aim of this project was to determine expression of miR-155, miR-19a, miR-181b, miR-24, relative to let-7a in sera of 63 patients with EBC and 21 healthy controls. Longitudinal multivariate data analysis was performed to stochastically model the serum levels of each of the oncomiRs during disease phases: from diagnosis, after surgery, and following chemo/radiotherapy. Moreover, this analysis was utilized to evaluate oncomiR levels in EBC patients subgrouped using current clinical prognostic factors including HER2, Ki-67, and grade III.

Results

EBC patients significantly over-express the oncomiRs at the time of diagnosis. Following surgical resection the serum levels of miR-155, miR-181b, and miR-24 significantly decreased (pā€‰=ā€‰1.89e-05, 5.41e-06, and 0.00638, respectively) whereas the miR-19a decreased significantly after the therapy (pā€‰=ā€‰0.00869). Furthermore, in case of high-risk patients serum levels of miR-155, miR-19a, miR-181b, and miR-24 are significantly more abundant in comparison to low-risk group (p = 0.026, 0.02567, 0.0250, and 0.00990) and show a decreasing trend upon therapy.

Conclusions

OncomiRs are significantly more abundant in the sera of EBC patients compared to controls at diagnosis. Differences in oncomiR levels reflecting EBC risk were also observed. Testing the oncomiRs may be useful for diagnostic purpose and possibly also for relapse detection in follow-up studies of EBC.

Keywords:
Breast cancer; microRNA; miR-155; miR-19a; miR-181b; miR-24; Let-7a