Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Comment
  • Published:

Unlocking the potential of urine-based liquid biopsy through improved reporting and standardization

Urine-based tumour DNA detection enables non-invasive profiling of urological malignancies and may also inform on distant cancers via trans-renal cell-free DNA. However, limited large-scale validation and standardization of urinary cell-free DNA biomarkers constrain their clinical use, highlighting the need for a reporting framework. We therefore propose the ‘minimal urine methods in experiments’ (MUMIE) framework.

This is a preview of subscription content, access via your institution

Access options

Buy this article

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Key preanalytical considerations in urine DNA biomarker research and clinical assays.

References

  1. Tivey, A. et al. Circulating tumour DNA - looking beyond the blood. Nat. Rev. Clin. Oncol. 19, 600–612 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Christensen, E. et al. Cell-free urine and plasma DNA mutational analysis predicts neoadjuvant chemotherapy response and outcome in patients with muscle-invasive bladder cancer. Clin. Cancer Res. 29, 1582–1591 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Green, E. et al. Clinical utility of cell-free and circulating tumor DNA in kidney and bladder cancer: a critical review of current literature. Eur. Urol. Oncol. 4, 893–903 (2021).

    Article  PubMed  Google Scholar 

  4. Li, F. et al. Utility of urinary circulating tumor DNA for EGFR mutation detection in different stages of non-small cell lung cancer patients. Clin. Transl. Oncol. 19, 1283–1291 (2017).

    Article  CAS  PubMed  Google Scholar 

  5. Pellini, B. et al. ctDNA MRD detection and personalized oncogenomic analysis in oligometastatic colorectal cancer from plasma and urine. JCO Precis. Oncol. https://doi.org/10.1200/PO.20.00276 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Cheng, T. et al. Genomewide bisulfite sequencing reveals the origin and time-dependent fragmentation of urinary cfDNA. Clin. Biochem. 50, 496–501 (2017).

    Article  CAS  PubMed  Google Scholar 

  7. Hentschel, A. et al. Comparative analysis of urine fractions for optimal bladder cancer detection using DNA methylation markers. Cancers 12, 859 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Markus, H. et al. Analysis of recurrently protected genomic regions in cell-free DNA found in urine. Sci. Transl. Med. 13, eaaz3088 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nikkola, J. et al. Sensitive detection of urothelial cancer via high-volume urine DNA analysis. Eur. Urol. 87, 86–88 (2024).

    Article  PubMed  Google Scholar 

  10. Augustus, E. et al. The art of obtaining a high yield of cell-free DNA from urine. PLoS ONE 15, e0231058 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Bosschieter, J. et al. A protocol for urine collection and storage prior to DNA methylation analysis. PLoS ONE 13, e0200906 (2018).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shekhtman, E. et al. Optimization of transrenal DNA analysis: detection of fetal DNA in maternal urine. Clin. Chem. 55, 723–729 (2009).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank K. Parekh for figure design, D. Gale, A. L’Hernault, R. Godin and R. Demers for expert insights, and M. Kushner for operational support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lars Dyrskjøt.

Ethics declarations

Competing interests

D.G.W. and R.T.B. receive royalties from Nonacus. R.D.M.S. is a minority shareholder of Self-screen BV. A.A.C. has issued and filed patents related to cancer biomarkers; has served as a consultant/advisor to Roche, Tempus, Guardant Health, Exact Sciences, Caris, Geneoscopy, Illumina, Myriad Genetics, Invitae, Daiichi Sankyo, AstraZeneca, AlphaSights, DeciBio and Guidepoint; has received honoraria from Agilent and Illumina; has received research support from Illumina, Roche and Tempus; has stock options in Geneoscopy; and has ownership interests in Droplet Biosciences, LiquidCell Dx and CytoTrace Biosciences. A.W.W. has served on advisory boards and/or received honoraria from AstraZeneca, Astellas, Bayer, EMD Serono, Janssen, Merck and Pfizer; and has contract research agreements (via institution) with ESSA Pharma, Tyra Biosciences and Promontory Therapeutics. L.D. has received research grants/support from Veracyte, C2i Genomics, Natera, AstraZeneca, Ferring and Photocure; has served as consultant for Ferring, UroGen, CystoTech, MSD and AstraZeneca; and has received speaker honoraria from Roche, Pfizer, and MSD. J.H., J.P.-B., D.M.V. and J.W. are employees of AstraZeneca. The other authors have no competing interest to declare.

Peer review

Peer review information

Nature Reviews Cancer thanks Muhammed Murtaza and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ward, D.G., Bryan, R.T., Chaudhuri, A.A. et al. Unlocking the potential of urine-based liquid biopsy through improved reporting and standardization. Nat Rev Cancer 26, 79–80 (2026). https://doi.org/10.1038/s41568-025-00882-z

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41568-025-00882-z

Search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer