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Molecular Diagnostics

CE–MS-based urinary biomarkers to distinguish non-significant from significant prostate cancer



Prostate cancer progresses slowly when present in low risk forms but can be lethal when it progresses to metastatic disease. A non-invasive test that can detect significant prostate cancer is needed to guide patient management.


Capillary electrophoresis/mass spectrometry has been employed to identify urinary peptides that may accurately detect significant prostate cancer. Urine samples from 823 patients with PSA (<15 ng/ml) were collected prior to biopsy. A case–control comparison was performed in a training set of 543 patients (nSig = 98; nnon-Sig = 445) and a validation set of 280 patients (nSig = 48, nnon-Sig = 232). Totally, 19 significant peptides were subsequently combined by a support vector machine algorithm.


Independent validation of the 19-biomarker model in 280 patients resulted in a 90% sensitivity and 59% specificity, with an AUC of 0.81, outperforming PSA (AUC = 0.58) and the ERSPC-3/4 risk calculator (AUC = 0.69) in the validation set.


This multi-parametric model holds promise to improve the current diagnosis of significant prostate cancer. This test as a guide to biopsy could help to decrease the number of biopsies and guide intervention. Nevertheless, further prospective validation in an external clinical cohort is required to assess the exact performance characteristics.

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E. Gómez-Gómez thanks The Carlos III Health Institute (ISCIII) and the European Social Funds (FSE) which funds his Rio Hortega research grant contract (CM16/00180). The biological samples repository node (Córdoba, Spain) is gratefully acknowledged for coordination tasks in the selection of urine samples. Ipek Guler from the methodology department of the Maimonides Institute of Biomedical Research of Cordoba is also gratefully acknowledged for collaboration in the statistical analysis.

Author information

M.F., E.G.G, H.M., and J.C.V. carried out the conception and design of the study; M.F., E.G.G., A.B.P., J.V.R. and J.C.V. contributed to the data acquisition; M.F., E.G.G., A.L., H.M. and J.C.V. carried out the analysis and interpretation of data; M.F. and E.G.G. drafted the paper; A.B.P., J.V.R., A.L., Z.C., A.S.M., R.M.L., M.J.R.T., H.M. and J.C.V. carried out a critical revision of the paper for important intellectual content; M.F. and A.L. performed the statistical analysis; R.M.L., M.J.R.T., H.M. and J.C.V. supervised the work.

Competing interests

H.M. is the founder and co-owner of Mosaiques Diagnostics. M.F. and A.L. are employed by Mosaiques Diagnostics.


This work was supported by The Spanish Ministerio de Economía y Competitividad (MINECO) and FEDER programme which are gratefully acknowledged for the financial support (Projects “Development of methods for early cancer detection; ONCOVER—detection system of volatile compounds for early diagnosis of lung, colon and prostate cancer”, CCB.030PM). This research was also supported in part by the BioGuidePCa (E! 11023, Eurostars) funded by BMBF (Germany) and PCaProTreat (H2020-MSCA-IF-2017-800048).

Ethics approval and consent to participate

This study was performed as part of the ONCOVER project. Ethical approval was obtained by the Reina Sofia Hospital Research Ethics Committee in accordance with the Declaration of Helsinki and informed consent was obtained from all participants for the project.

Data availability

All data generated or analysed during this study are included in this published article.


This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Correspondence to Julia Carrasco Valiente.

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