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