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Platinum Priority – Testis Cancer
Editorial by XXX on pp. x–y of this issue

Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours

By: Klaus-Peter Dieckmanna , Arlo Radtkeb , Meike Spiekermannb , Thomas Balksa, Cord Matthiesc, Pascal Beckerc, Christian Rufc, Christoph Oingd, Karin Oechsled, Carsten Bokemeyerd, Johannes Hammele, Sebastian Melchiore, Werner Wosniokf and Gazanfer Belgeb

European Urology, Volume 71 Issue 2, February 2017, Pages 213-220

Published online: 01 February 2017

Keywords: Germ cell tumour, MicroRNA, Seminoma, Serum biomarker, Teratoma, Testis

Abstract Full Text Full Text PDF (2,0 MB)

Abstract

Background

Clinical management of germ cell tumours (GCTs) relies on monitoring of serum tumour markers. However, the markers α-fetoprotein (AFP), the β-subunit of human chorionic gonadotropin (bHCG), and lactate dehydrogenase (LDH) are expressed in <60% of GCT cases.

Objective

To test the utility of the microRNAs (miRNAs) miR-371a-3p, miR-372-3p, miR-373-3p, and miR-367-3p as sensitive and specific GCT serum biomarkers.

Design, setting, and participants

Serum levels of miRNAs were measured in 166 consecutive patients with GCT before and after treatment and in 106 male controls. In the first 50 consecutive patients, all four miRNAs were measured. In the main study, only the most sensitive miRNA was further analysed.

Outcome measurements and statistical analysis

The specificity and sensitivity of the four miRNAs were studied using receiver operating characteristic curves. miRNA sensitivities were compared to those of classical markers. Statistical cross-comparisons of miRNA levels for GCT subgroups and controls were performed at various time points during treatment.

Results and limitations

Overall, miR-371a-3p performed best, with 88.7% sensitivity (95% confidence interval [CI] 82.5–93.3%) and 93.4% specificity (95% CI 86.9–97.3%) and an area under the curve of 0.94, outperforming AFP, bHCG, and LDH (combined sensitivity 50%). According to Kernel density estimation, the sensitivity and specificity were 86.3% and 92.5%, respectively. miR-371a-3p levels dropped to normal after completion of treatment. The miRNA levels correlated with treatment failure and relapse. Teratoma did not express miR-371a-3p.

Conclusions

The miRNA miR-371a-3p is a specific and sensitive novel serum GCT biomarker that accurately correlates with disease activity. Validation of this test in a large-scale prospective study is needed.

Patient summary

miR-371a-3p is a novel serum marker for germ cell tumours that is expressed by 88.7% of patients and thus is far more sensitive and specific than classical serum markers. It correlates with tumour burden and treatment results. Validation in a large patient cohort is needed.

Take Home Message

Serum microRNA-371a-3p represents a sensitive and specific novel serum biomarker for germ cell tumours that accurately correlates with clinical stage and treatment effects. In contrast to the classical bHCG and AFP markers, miR-371a-3p is also expressed in seminoma.

Keywords: Germ cell tumour, MicroRNA, Seminoma, Serum biomarker, Teratoma, Testis.

Footnotes

a Department of Urology, Albertinen Krankenhaus, Hamburg, Germany

b Centre for Human Genetics, University of Bremen, Bremen, Germany

c Department of Urology, Bundeswehr Krankenhaus, Hamburg, Germany

d Department of Medical Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany

e Department of Urology, Zentralklinikum Bremen, Bremen, Germany

f Institute of Statistics, University of Bremen, Bremen, Germany

Corresponding author. Department of Urology, Albertinen Krankenhaus, Suentelstrasse 11a, D-22457 Hamburg, Germany. Tel. +40 55 882253; Fax: +40 55 882381.

These authors contributed equally to this work.

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