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  • Review Article
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Developing proteomic biomarkers for bladder cancer: towards clinical application

Nature Reviews Urology volume 12, pages 317–330 (2015)Cite this article

Subjects

Key Points

  • An unmet clinical need exists for accurate, noninvasive assays, which enable the accurate diagnosis of bladder cancer and monitoring of patients for recurrence

  • Urine is the most appropriate bodily fluid for biomarker research owing to its noninvasive and easy collection, stability of samples and proximity to bladder tumours

  • Proteomics platforms have the advantages of providing large datasets with numerous putative biomarker candidates at high resolution; these technologies might also potentially enable validation of biomarker candidates

  • Multiple biomarker panels are likely to be more effective than single biomarkers, owing to the high level of disease heterogeneity observed among patients with bladder cancer

  • Multiple proteomic biomarkers for bladder cancer have already been discovered; however, a lack of validation in the appropriate patient populations and in specific contexts of use precludes clinical implementation

Abstract

Clinical use of proteomic biomarkers has the potential to substantially improve the outcomes of patients with bladder cancer. An unmet clinical need evidently exists for noninvasive biomarkers, which might enable improvements in both the diagnosis and prognosis of patients with bladder cancer, as well as improved monitoring of patients for the presence of recurrence. Urine is considered the optimal noninvasive source of proteomic biomarkers in patients with bladder cancer. Currently, a number of single-protein biomarkers have been detected in urine and tissue using a variety of proteomic techniques, each having specific conceptual considerations and technical implications. Promising preclinical data are available for several of these proteins; however, the combination of single urinary proteins into multimarker panels might better encompass the molecular heterogeneity of bladder cancer within this patient population, and prove more effective in clinical use.

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Figure 1: Overview of the biomarker development workflow.

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Acknowledgements

The work is supported in part by the BCMolMed grant (PITN-GA-2012-317,450) from the FP7–PEOPLE–2012–ITN programme and TransBioBC grant (601,933) from the FP7-Health project funded by the European Commission.

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Authors and Affiliations

  1. Biotechnology Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, Athens, 115 27, Greece

    Maria Frantzi, Agnieszka Latosinska, Elena Critselis & Antonia Vlahou

  2. Mosaiques Diagnostics GmbH, Rotenburger Strasse 20, Hannover, 30659, Germany

    Leif Flühe

  3. Department of Urology and Urological Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, Hannover, 30625, Germany

    Marie C. Hupe, Mario W. Kramer & Axel S. Merseburger

  4. BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Avenue, Glasgow, G12 8TA, UK

    Harald Mischak

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  1. Maria Frantzi
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Contributions

M.F., A.L. and L.F. researched data for the article, M.F. and A.L. wrote the article, M.C.H., M.W.K., A.S.M., H.M. and A.V. made a substantial contribution to discussions of content, M.F., A.L., E.C., H.M. and A.V. reviewed and/or edited the manuscript before submission. M.F. and A.L. contributed equally, and should be considered equal first authors.

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Correspondence to Maria Frantzi.

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Competing interests

H.M. is the founder and co-owner of Mosaiques Diagnostics. M.F. is employed by Mosaiques Diagnostics as part of an EID (Industrial-Academia) Marie Curie Action. L.F. is employed by Mosaiques Diagnostics. The other authors declare no competing interests.

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Frantzi, M., Latosinska, A., Flühe, L. et al. Developing proteomic biomarkers for bladder cancer: towards clinical application. Nat Rev Urol 12, 317–330 (2015). https://doi.org/10.1038/nrurol.2015.100

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