Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours
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Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours. / Dieckmann, Klaus-Peter; Radtke, Arlo; Spiekermann, Meike; Balks, Thomas; Matthies, Cord; Becker, Pascal; Ruf, Christian; Oing, Christoph; Oechsle, Karin; Bokemeyer, Carsten; Hammel, Johannes; Melchior, Sebastian; Wosniok, Werner; Belge, Gazanfer.
in: EUR UROL, Jahrgang 71, Nr. 2, 02.2017, S. 213-220.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours
AU - Dieckmann, Klaus-Peter
AU - Radtke, Arlo
AU - Spiekermann, Meike
AU - Balks, Thomas
AU - Matthies, Cord
AU - Becker, Pascal
AU - Ruf, Christian
AU - Oing, Christoph
AU - Oechsle, Karin
AU - Bokemeyer, Carsten
AU - Hammel, Johannes
AU - Melchior, Sebastian
AU - Wosniok, Werner
AU - Belge, Gazanfer
N1 - Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
PY - 2017/2
Y1 - 2017/2
N2 - 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.
AB - 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.
U2 - 10.1016/j.eururo.2016.07.029
DO - 10.1016/j.eururo.2016.07.029
M3 - SCORING: Journal article
C2 - 27495845
VL - 71
SP - 213
EP - 220
JO - EUR UROL
JF - EUR UROL
SN - 0302-2838
IS - 2
ER -