MicroRNAs in tumor samples and urinary extracellular vesicles as a putative diagnostic tool for muscle-invasive bladder cancer

Abstract

Purpose

The identification of biomarkers characterizing the invasive potential of bladder cancer could enhance the clinical management of individual patients and therefore improve prognosis. The aim of this study was to define a miRNA panel in tumor tissues as well as in urinary extracellular vesicles (EVs) for discriminating muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC).

Methods

miRNA expression was analyzed in 24 formalin-fixed, paraffin-embedded (FFPE) tumor samples by microarray analysis and was further validated by qRT-PCR in 56 FFPE tumor samples as well as in 37 urinary EV samples.

Results

Microarray analysis revealed 63 miRNAs that were significantly differentially expressed (P < 0.05) between tissues from MIBC and NMIBC tumors. Five selected miRNAs (miR-146b-5p, miR-155-5p, miR-138-5p, miR-144-5p, and miR-200a-3p) were validated by qRT-PCR. The expression of all except miR-144-5p was significantly associated with high tumor grade. In urinary EVs, a different expression was verified for miR-146b-5p (P = 0.004) and miR-155-5p (P = 0.036), which exhibited significantly higher expression in urinary EVs from patients with MIBC.

Conclusions

miRNAs are promising biomarkers for the identification of invasive bladder carcinomas. Tissue samples as well as urinary EVs may serve as sources for miRNA analysis. This method, in addition to histopathology, could provide a new diagnostic tool and facilitate individual therapeutic decisions to select patients for early cystectomy.

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Acknowledgements

We gratefully acknowledge Laura Witt, Alexander Vogt and Sebastian Hölters from our department for excellent technical support.

Funding

Funding was received from Saarland University, Saarbrücken, Germany, for the microarray analysis of tumor tissues and partially for the RT-PCR validation of tumor tissues and EVs.

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Authors

Contributions

SB and KJ contributed to the study conception and design. MS, SB and KJ contributed to the patient assessment and recruitment and sample collection. AP and RB contributed to the pathological diagnosis. SB, JH, PM and PE contributed to the molecular biology analyses. SB, KJ, JH, PM, PE, JuH and MS contributed to the statistical analyses and data interpretation. SB, KJ, JuH and MS contributed to the manuscript drafting and intellectual input. SB, KJ, JuH and MS contributed to the writing of the final manuscript version. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Kerstin Junker.

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The authors declare that they have no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Cite this article

Baumgart, S., Meschkat, P., Edelmann, P. et al. MicroRNAs in tumor samples and urinary extracellular vesicles as a putative diagnostic tool for muscle-invasive bladder cancer. J Cancer Res Clin Oncol 145, 2725–2736 (2019). https://doi.org/10.1007/s00432-019-03035-6

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Keywords

  • Bladder cancer
  • Muscle-invasive bladder cancer
  • microRNA
  • Extracellular vesicle
  • Urine