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Molecular Diagnostics

Multicentric validation of diagnostic tests based on BC-116 and BC-106 urine peptide biomarkers for bladder cancer in two prospective cohorts of patients

British Journal of Cancer volume 127, pages 2043–2051 (2022)Cite this article

Subjects

Abstract

Background

Non-invasive urine-based biomarkers can potentially improve current diagnostic and monitoring protocols for bladder cancer (BC). Here we assess the performance of earlier published biomarker panels for BC detection (BC-116) and monitoring of recurrence (BC-106) in combination with cytology, in two prospectively collected patient cohorts.

Methods

Of the 602 patients screened for BC, 551 were found eligible. For the primary setting, 73 patients diagnosed with primary BC (n = 27) and benign urological disorders, including patients with macroscopic haematuria, cystitis and/or nephrolithiasis (n = 46) were included. In total, 478 patients under surveillance were additionally considered (83 BC recurrences; 395 negative for recurrence). Urine samples were analysed with capillary electrophoresis-mass spectrometry. The biomarker score was estimated via support vector machine-based software.

Results

Validation of BC-116 biomarker panel resulted in 89% sensitivity and 67% specificity (AUCBC-116 = 0.82). A diagnostic score based on cytology and BC-116 resulted in good (AUCNom116 = 0.85) but not significantly better performance (P = 0.5672). A diagnostic score including BC-106 and cytology was evaluated (AUCNom106 = 0.82), significantly outperforming both cytology (AUCcyt = 0.72; P = 0.0022) and BC-106 (AUCBC-106 = 0.67; P = 0.0012).

Conclusions

BC-116 biomarker panel is a useful test for detecting primary BC. BC-106 classifier integrated with cytology showing >95% negative predictive value, might be useful for decreasing the number of cystoscopies during surveillance.

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Fig. 1: Schematic representation of the study workflow.
Fig. 2: Performance characteristics of the urinary biomarkers in the primary cohort including 73 patients.
Fig. 3: Comparative ROC curve analyses for the urinary biomarkers and the cytology.
Fig. 4: Comparative ROC curve analyses for the urinary biomarkers and the cytology for the recurrence cohort.
Fig. 5: Performance characteristics of the integrative diagnostic score in the recurrence cohort.

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Data availability

All data (except raw files) generated or analysed during this study are included in this article (and its supplementary information files). Raw data are available upon request from the corresponding author.

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Funding

This work was supported by BioMedBC (752755; H2020-MSCA-IF-2016) a programme funded by the European Commission (EC) under Marie Sklodowska-Curie actions (MSCA) H2020 Work Programme. The specific role of the funding organisation (EC) was to financially support the acquisition of the data and part of the data analysis.

Author information

Authors and Affiliations

  1. Laboratory and Department of Urology, Hospital Clinic de Barcelona, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

    Lourdes Mengual, Mercedes Ingelmo-Torres & Antonio Alcaraz

  2. Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Barcelona, Barcelona, Spain

    Lourdes Mengual

  3. Department of Biomarker Research, Mosaiques Diagnostics, Hannover, Germany

    Maria Frantzi, Marika Mokou & Harald Mischak

  4. Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands

    Michiel Vlaming & Antoine G. Van der Heijden

  5. University Hospital Schleswig-Holstein, Campus Lübeck, Department of Urology, Lübeck, Germany

    Axel S. Merseburger & Marie C. Roesch

  6. Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria

    Zoran Culig

  7. Systems Biology Center, Biomedical Research Foundation, Academy of Athens, Athens, Greece

    Antonia Vlahou

  8. Institute of Cardiovascular and Medical Science, University of Glasgow, Glasgow, UK

    Harald Mischak

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  1. Lourdes Mengual
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Contributions

AGVdH had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: LM, MF, AV, HM and AGVdH; acquisition of the data: LM, MF, MI-T and MV; analysis and interpretation of the data: LM, MF, MM, MI-T, MV; drafting of the manuscript: LM, MF, MM; critical revision of the manuscript for important intellectual content: LM, MF, MM, MI-T, MV, ASM, MCR, ZC, AA, AV, HM and AGVdH; statistical analysis: LM, MF and MM; obtaining funding: MF; administrative, technical or material support: LM, AA, AV, HM and AGVdH; supervision: LM, ASM, MCR, ZC, AA, HM and AGVdH; other/software validation: MF and MM.

Corresponding author

Correspondence to Maria Frantzi.

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Competing interests

Prof. HM holds ownership interest in Mosaiques Diagnostics GmbH. Dr. MF and Dr. MM are employed by Mosaiques Diagnostics GmbH. The remaining authors declare no competing interests.

Ethics approval and consent to participate

Informed consent forms were obtained and adhered to Institutional Review Board-approved guidelines. Ethical approval for this study was obtained by the Ethics Committee in Medical School of Hannover (ID:3274–2016). The study was performed in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Mengual, L., Frantzi, M., Mokou, M. et al. Multicentric validation of diagnostic tests based on BC-116 and BC-106 urine peptide biomarkers for bladder cancer in two prospective cohorts of patients. Br J Cancer 127, 2043–2051 (2022). https://doi.org/10.1038/s41416-022-01992-3

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