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Urinary Exosomal MicroRNAs as Potential Non-invasive Biomarkers in Breast Cancer Detection

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Abstract

Introduction

Breast cancer (BC) is the most frequent malignant disease in women worldwide and is therefore challenging for the healthcare system. Early BC detection remains a leading factor that improves overall outcome and disease management. Aside from established screening procedures, there is a constant demand for additional BC detection methods. Routine BC screening via non-invasive liquid biopsy biomarkers is one auspicious approach to either complete or even replace the current state-of-the-art diagnostics. The study explores the diagnostic potential of urinary exosomal microRNAs with specific BC biomarker characteristics to initiate the potential prospective application of non-invasive BC screening as routine practice.

Methods

Based on a case–control study (69 BC vs. 40 healthy controls), expression level quantification and subsequent biostatistical computation of 13 urine-derived microRNAs were performed to evaluate their diagnostic relevance in BC.

Results

Multilateral statistical assessment determined and repeatedly confirmed a specific panel of four urinary microRNA types (miR-424, miR-423, miR-660, and let7-i) as a highly specific combinatory biomarker tool discriminating BC patients from healthy controls, with 98.6% sensitivity and 100% specificity.

Discussion

Urine-based BC diagnosis may be achieved through the analysis of distinct microRNA panels with proven biomarker abilities. Subject to further validation, the implementation of urinary BC detection in routine screening offers a promising non-invasive alternative in women’s healthcare.

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Data Availability

All data generated or analyzed during this study are included in this published article and its supplementary information files. Additional information is available from the corresponding author on reasonable request.

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Acknowledgements

The authors are particularly grateful for the continuous organizational support and technical assistance given by Mrs. Claudia Nöthling.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Medical Center, University of Freiburg, Freiburg, Germany

    Marc Hirschfeld, Daniela Weiß, Kai Berner, Andrea Ritter, Markus Jäger & Thalia Erbes

  2. Faculty of Medicine, University of Freiburg, Freiburg, Germany

    Marc Hirschfeld, Gerta Rücker, Daniela Weiß, Kai Berner, Andrea Ritter, Markus Jäger & Thalia Erbes

  3. Institute of Veterinary Medicine, Georg-August-University Goettingen, Goettingen, Germany

    Marc Hirschfeld

  4. Institute of Medical Biometry and Statistics, Medical Center, University of Freiburg, Freiburg, Germany

    Gerta Rücker

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Contributions

TE, MJ, and MH devised the project outline and experimental study concept. MJ substantially worked out technical details of analytical assays. MJ, DW, and AR performed practical realization of sample handling, processing, and data acquisition. DW and AR were responsible for study-relevant patient data administration. TE, MJ, MH, and DW conducted a collective literature review. GR conceptually designed and overall guided statistical data assessment. GR performed statistical testing to extract decisive informative value. Final data evaluation and determination of conclusive study output were performed by MH, TE, GR, and MJ. MH, TE, and GR wrote the manuscript in consultation with and under critical revision of KB, MJ, DW, and AR. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Thalia Erbes.

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Conflict of interest

The authors TE, MJ, DW, and MH declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, excepting that they are listed as innovators with respect to a patent submitted to the European Patent Office by the University of Freiburg in 08/2019, with a currently pending patent application status (application No. EP19190989.4). The authors GR, AR, and KB declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethics approval and consent to participate

The according investigation protocols (36/12 and 386/16) were approved by the institutional ethical review board of the University of Freiburg. All patients and healthy controls involved provided written informed consent in accordance with the Declaration of Helsinki.

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Hirschfeld, M., Rücker, G., Weiß, D. et al. Urinary Exosomal MicroRNAs as Potential Non-invasive Biomarkers in Breast Cancer Detection. Mol Diagn Ther 24, 215–232 (2020). https://doi.org/10.1007/s40291-020-00453-y

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