MicroRNAs from urinary exosomes as alternative biomarkers in the differentiation of benign and malignant prostate diseases

Jonas Holdmann; Lukas Markert; Claudia Klinger; Michael Kaufmann; Karin Schork; Michael Turewicz; Martin Eisenacher; Stephan Degener; Nici M. Dreger; Stephan Roth; Andreas Savelsbergh

doi:10.33393/jcb.2022.2317

Authors

Jonas Holdmann Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten - Germany
Lukas Markert Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten - Germany https://orcid.org/0000-0002-1739-3619
Claudia Klinger Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten and Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Witten - Germany https://orcid.org/0000-0002-6085-9584
Michael Kaufmann Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten and Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Witten - Germany https://orcid.org/0000-0001-7595-1386
Karin Schork Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum and Center for Protein Diagnostics (PRODI), Medical Proteome Analysis, Ruhr-University, Bochum - Germany https://orcid.org/0000-0003-3756-4347
Michael Turewicz Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum and Center for Protein Diagnostics (PRODI), Medical Proteome Analysis, Ruhr-University, Bochum - Germany https://orcid.org/0000-0003-0737-1114
Martin Eisenacher Medizinisches Proteom-Center, Ruhr-University Bochum, Bochum and Center for Protein Diagnostics (PRODI), Medical Proteome Analysis, Ruhr-University, Bochum - Germany https://orcid.org/0000-0003-2687-7444
Stephan Degener Department of Urology, Helios University Hospital Wuppertal, Center for Clinical and Translational Research, Witten/Herdecke University, Wuppertal - Germany https://orcid.org/0000-0003-4428-7202
Nici M. Dreger Department of Urology, Helios University Hospital Wuppertal, Center for Clinical and Translational Research, Witten/Herdecke University, Wuppertal - Germany https://orcid.org/0000-0002-2153-7371
Stephan Roth Department of Urology, Helios University Hospital Wuppertal, Center for Clinical and Translational Research, Witten/Herdecke University, Wuppertal - Germany
Andreas Savelsbergh Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten and Center for Biomedical Education and Research (ZBAF), Witten/Herdecke University, Witten - Germany https://orcid.org/0000-0002-6136-3230

DOI:

https://doi.org/10.33393/jcb.2022.2317

Keywords:

Biomarker, Extracellular vesicles, Liquid biopsy, microRNA, Prostate cancer, Urine

Abstract

Introduction: Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth most cancer-related cause of death worldwide. Various tools are used in the diagnosis of PCa, such as the Prostate-Specific Antigen (PSA) value or digital rectal examination. A final differentiation from benign prostate diseases such as benign prostatic hyperplasia (BPH) can often only be made by a transrectal prostate biopsy. This procedure carries post-procedural complications for the patients and may lead to hospitalization.

Urinary exosomes contain unique components, such as microRNAs (miRNAs) with information about their original tissue. As miRNAs appear to play a role in the development of PCa, they might be useful to develop procedures that could potentially make transrectal biopsies avoidable in certain situations.

Methods: The current study aimed to investigate whether miRNAs from urinary exosomes can be used to differentiate PCa from BPH. For this purpose, urine samples from 28 patients with PCa and 25 patients with BPH were collected and analysed using next-generation sequencing to obtain expression profiles.

Results and conclusion: The two miRNAs hsa-miR-532-3p and hsa-miR-6749-5p showed a significant differential expression within the group of patients with PCa in a training subset of the data containing 32 patients. They were further validated on the independent test data subset containing 20 patients. Additionally, a machine learning algorithm was used to generate a miRNA pattern to distinguish the two disease entities. Both approaches seem to be suitable for the search of alternative diagnostic tools for the differentiation of benign and malignant prostate diseases.

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Author Biographies

Jonas Holdmann, Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten - Germany

* Contributed equally

Lukas Markert, Chair for Biochemistry and Molecular Medicine, Division of Functional Genomics, Witten/Herdecke University, Witten - Germany

* Contributed equally

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