Skip to main content
Log in

Urindiagnostik – die neue Liquid Biopsy

Urinalysis: the new liquid biopsy

  • Leitthema
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

Hintergrund

In der Onkologie ist die Liquid Biopsy neben dem Tumorzellnachweis vor allem auf blutbasierte Analysen von Nukleinsäuren fokussiert, die den Nachweis von Tumorzellen oder Tumor-DNA ermöglichen. Mögliche Anwendungen sind das Screening zur Früherkennung, das Therapiemonitoring, prognostische Biomarker und der Nachweis erworbener Mutationen zur zielgerichteten Therapiewahl.

Fragestellung

Die urinbasierte Liquid Biopsy bietet gegenüber der blutbasierten potenzielle Vorteile. Urin steht in großen Mengen zu Verfügung und lässt sich nichtinvasiv gewinnen. Kann eine Liquid Biopsy aus Urin mit Messung von Tumor-miRNA („micro RNA“), -Exosomen, -ctDNA („circulating tumor DNA“) und Proteomanalysen Ergebnisse wie die blutbasierten Analysen mit klinischer Nutzbarkeit liefern?

Material und Methoden

Eine systematische Literatursuche wurde in PubMed unter Berücksichtigung von Einzelarbeiten, Reviews und Metaanalysen durchgeführt.

Ergebnisse

Die Studien an kleinen, retrospektiven Kohorten zeigen, dass die urinbasierte Liquid Biopsy technisch machbar ist und spezifische Muster (miRNA, Exosome, Proteom, ctDNA) als diagnostische Biomarker Patientinnen mit Präkanzerosen des Zervixkarzinoms sowie manifesten Mamma, Ovarial- und Endometriumkarzinomen identifizieren. Therapiemonitoring und der Nachweis von Genmutationen, die therapeutische Targets darstellen, sind möglich. Auch in der Geburtshilfe zeigen sich Indikationen, z. B. für den Nachweis eines GDM (Gestationsdiabetes) oder einer intrahepatischen Cholestase.

Schlussfolgerungen

Mit weiteren Anwendungsindikationen, zunehmender Standardisierung der Probenverarbeitung sowie prospektiven Studien bietet die urinbasierte Liquid Biopsy ein großes Potenzial für den klinischen Einsatz.

Abstract

Background

In oncology, liquid biopsy focusses, in addition to the detection of tumour cells, mainly on the blood-based analysis of nucleic acids to identify tumour cells as well as tumour DNA. Potential indications include screening for cancer, monitoring of treatment, use as a prognostic biomarker and detection of newly acquired mutations for targeted treatment.

Objectives

Urine-based liquid biopsy offers potential advantages over blood-based analyses. Urine is available in large quantities and can be collected by non-invasive methods. Is urinary liquid biopsy able to measure miRNA, exosomes, ctDNA and the proteomic pattern of tumors with a sensitivity and specificity comparable to blood-based analyses, thereby providing clinical utility?

Methods

A systematic review of the literature in Pubmed was performed using the search term urinary liquid biopsy and taking into account single studies, reviews and meta-analyses.

Results

The small, and mostly retrospective, studies showed that urinary liquid biopsy is technically feasible and that specific patterns (miRNA, exosomes, proteom, ctDNA) as diagnostic biomarkers identify patients with precancerous lesions of the cervix, as well as with invasive breast, ovarian and endometrial cancer. Monitoring of oncological treatments, as well as detection of specific mutations as potential therapeutic targets, is possible. In addition, promising indications for the technology were identified in obstetrics, such as the verification of gestational diabetes or intrahepatic cholestasis of pregnancy.

Conclusions

With further indications, the increasing standardization of sample processing and growing numbers of prospective studies, urinary liquid biopsy offers great potential for its clinically useful deployment in practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Literatur

  1. Ando W, Kikuchi K, Uematsu T et al (2019) Novel breast cancer screening: combined expression of miR-21 and MMP‑1 in urinary exosomes detects 95 % of breast cancer without metastasis. Sci Rep 9:13595

    Article  Google Scholar 

  2. Beretov J, Wasinger VC, Milar EK et al (2015) Proteomic analysis of urine to identify breast cancer biomarker candidates using label-free LC-MS/MS approach. PLoS ONE 10:e141876

    Article  Google Scholar 

  3. Cai Y, Yu X, Hu S et al (2009) A brief review on the mechanisms of miRNA regulation. Genomics Proteomics Bioinformatics 7(4):147–154

    Article  CAS  Google Scholar 

  4. Erbes T, Hirschfeld M, Rücker G et al (2015) Feasibilty of urinary micro RNA detection in breast cancer patients and its potential as an innovative non-invasive biomarker. BMC Cancer 15:193

    Article  Google Scholar 

  5. Gasparri ML, Casorelli A, Bardhi E et al (2018) Beyond circulating microRNA biomarkers: urinary micorRNas in ovarian and breast cancer. Tumour Biol 39:1010428317695525

    Google Scholar 

  6. Hamam R, Hamam D, Alsaleh KA et al (2017) Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers. Cell Death Dis 8(9):e3045

    Article  Google Scholar 

  7. Herrera-Van Oostdam AS, Toro-Ortiz JC, López J et al (2020) Placental exosomes isolated from urine of patients with gestational diabetes exhibit a differential profile expression of microRNA across gestation. Int J Mol Med 46:546–560

    Article  CAS  Google Scholar 

  8. Hesari AR, Golrokh Moghadam SA, Siasi AS et al (2018) Tumor derived exosomes. J Cell Biochem 119:4236–4240

    Article  CAS  Google Scholar 

  9. Jiang PY, Zhu XJ, Jiang RA et al (2019) Micro RNAs derived from urinary exosomes act as novel biomarkers in the diagnosis of intrahepatic cholestasis of pregnancy. Am J Transl Res 11:6249–6261

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Kim H, Min HK, Kong G (2009) Quantitative analysis of phosphatidylcholines and phosphatidylethanolamines in urine of patients with breast cancer by nanoflow liquid chromatography/tandem mass spectrometry. Anal Bioanal Chem 393(6–7):1649–1656

    Article  CAS  Google Scholar 

  11. Kok VC, Yu C‑C (2020) Cancer derived exosomes: their role in cancer biology and biomarker development Int J of. Nanomedicine 15:8019–8036

    CAS  Google Scholar 

  12. Magbanua MJM, Swigart LB, Wu HT et al (2020) Circulating tumor DNA in neoadjuvant-treated breast cancer reflects response und survival. Ann Oncol 32(2):229–239. https://doi.org/10.1016/j.annonc.2020.11.007

    Article  PubMed  Google Scholar 

  13. Mistry DA, French P (2016) Circulating phospholipids as biomarkers of breast cancer: a review. Breast Cancer (Auckl) 3:191–196

    Google Scholar 

  14. Moreau K, Dizin E, Hind R et al (2006) BRCA1 affects lipid synthesis through its interaction with acetyl-CoA carboxylase. J Biol Chem 281(6):3172–3178

    Article  CAS  Google Scholar 

  15. Narouzi-Barough L, Koshro Shahi AA, Mohebzadeh F et al (2020) Early diagnosis of breast and ovarian cancers by body fluids circulating tumor-derived exosomes. Cancer Cell Int 20:187

    Article  Google Scholar 

  16. Pantel K, Mader S (2017) Liquid biopsy:current status and future perspectives. Oncol Res Treat 40:404–408

    Article  Google Scholar 

  17. Pathak N, Dodds J, Zamora J et al (2014) Accuracy of urinary human papilloma testing for presence of cervical HPV: systematic review and meta-analysis. BMJ 349:g5264

    Article  Google Scholar 

  18. Ritter A, Hirschfeld M, Berner K et al (2020) Circulation non coding RNA biomarker potential in neoadjuvant chemotherapy of triple negative breast cancer. Int J Oncol 56:47–86

    CAS  PubMed  Google Scholar 

  19. Srivastava SK, Ahmad A et al (2017) MicroRNAs in gynecological cancers: small molecules with big implications. Cancer Lett 407:123–138

    Article  CAS  Google Scholar 

  20. Santos JC, da Silva Lima N, Sarian LO et al (2018) Exosome-mediated breast cancer chemoresistance via miR-155 transfer. Sci Rep 8:829

    Article  Google Scholar 

  21. Slupsky CM, Steed H, Wells TU et al (2010) Urine metabolite analysis offers potential early diagnosis of ovarian and breast cancer. Clin Cancer Res 16(23):5835–5841

    Article  CAS  Google Scholar 

  22. Srivastava A, Moxley K, Ruskin R et al (2018) A non-invasive liquid biopsy screening of urine-derived exosomes for miRNAs as biomarker in endometrial cancer patients. AAPS J 20:82

    Article  Google Scholar 

  23. Steenbergen RDM, Snijders PJ, Heideman DAM et al (2014) Clinical implication of (epi)genetic changes in HPV-induced cervical precancerous lesions. Nat Rev Cancer 14:395–405

    Article  CAS  Google Scholar 

  24. Turchinovich A, Weiz L, Burwinkel B (2012) Extracellular miRNAs in Serum: the mystery of their origin and function. Trends Biochem Sci 37:460–465

    Article  CAS  Google Scholar 

  25. Van Keer S, Pattyn J, Tjalma WAA (2017) First-void urine: a potential biomarker source for triage of high-risk human papillomavirus infected women. Eur J Obstet Gynecol Reprod Biol 216:1–11

    Article  Google Scholar 

  26. Vickers KC, Palmisano BT, Shoucri BM et al (2011) Micro RNA are transported in plasma and delivered to recipient cells in high density lipoproteins. Nat Cell Biol 13:324–422

    Article  Google Scholar 

  27. Young-Kook K (2015) Extracellular microRNAs as biomarkers in human disease. Chonnam Med J 51:51–57

    Article  Google Scholar 

  28. Zhang S, Lu Z, Unruh AK et al (2015) Clinically relevant microRNAs in ovarian cancer. Mol Cancer Res 13:393–401

    Article  CAS  Google Scholar 

  29. Zhou J, Gong G, Tan H et al (2015) Urinary microRNA 30a-5p is a potential biomarker for ovarian serous adenocarcinoma. Oncol Rep 33:2915–2923

    Article  CAS  Google Scholar 

  30. Zuo Z, Tang J, Cai X (2020) Probing breast cancer using a combination of plasma and urinary circulating cell-free DNA. Biosci Rep 40:BSR20194306

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Elmar Stickeler.

Ethics declarations

Interessenkonflikt

E. Stickeler gibt an, dass er ein Patent für eine miRNA-Profil aus Urin zur Detektion von Brustkrebs hält. Ansonsten bestehen keine Interessenkonflikte.

Für diesen Beitrag wurden von den Autoren keine Studien an Menschen oder Tieren durchgeführt. Für die aufgeführten Studien gelten die jeweils dort angegebenen ethischen Richtlinien.

Additional information

Redaktion

T. Fehm, Düsseldorf

W. Jonat, Kiel

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Stickeler, E. Urindiagnostik – die neue Liquid Biopsy. Gynäkologe 54, 175–180 (2021). https://doi.org/10.1007/s00129-021-04749-w

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00129-021-04749-w

Schlüsselwörter

Keywords

Navigation