title: Serum Levels of MicroRNA miR-371a-3p: A Sensitive and Specific New Biomarker for Germ Cell Tumours.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Urology, Albertinen Krankenhaus, Hamburg, Germany. Electronic address: dieckmannkp@t-online.de.
authors: Klaus-Peter
authors: KP
authors: Dieckmann
authors: Centre for Human Genetics, University of Bremen, Bremen, Germany.
authors: Arlo
authors: A
authors: Radtke
authors: Centre for Human Genetics, University of Bremen, Bremen, Germany.
authors: Meike
authors: M
authors: Spiekermann
authors: Department of Urology, Albertinen Krankenhaus, Hamburg, Germany.
authors: Thomas
authors: T
authors: Balks
authors: Department of Urology, Bundeswehr Krankenhaus, Hamburg, Germany.
authors: Cord
authors: C
authors: Matthies
authors: Department of Urology, Bundeswehr Krankenhaus, Hamburg, Germany.
authors: Pascal
authors: P
authors: Becker
authors: Department of Urology, Bundeswehr Krankenhaus, Hamburg, Germany.
authors: Christian
authors: C
authors: Ruf
authors: Department of Medical Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors: Christoph
authors: C
authors: Oing
authors: Department of Medical Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors: Karin
authors: K
authors: Oechsle
authors: Department of Medical Oncology, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
authors: Carsten
authors: C
authors: Bokemeyer
authors: Department of Urology, Zentralklinikum Bremen, Bremen, Germany.
authors: Johannes
authors: J
authors: Hammel
authors: Department of Urology, Zentralklinikum Bremen, Bremen, Germany.
authors: Sebastian
authors: S
authors: Melchior
authors: Institute of Statistics, University of Bremen, Bremen, Germany.
authors: Werner
authors: W
authors: Wosniok
authors: Centre for Human Genetics, University of Bremen, Bremen, Germany.
authors: Gazanfer
authors: G
authors: Belge
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood; D006801:Humans; D007984:Leydig Cell Tumor / Q000097:blood*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood*; D012680:Sensitivity and Specificity; D013736:Testicular Neoplasms / Q000097:blood*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C568081:MIRN367 microRNA, human; C554834:MIRN371 microRNA, human; C561021:MIRN372 microRNA, human; C527114:MIRN373 microRNA, human; D035683:MicroRNAs
keywords: Germ cell tumour; MicroRNA; Seminoma; Serum biomarker; Teratoma; Testis