title: Circulating serum miRNA (miR-367-3p, miR-371a-3p, miR-372-3p and miR-373-3p) as biomarkers in patients with testicular germ cell cancer.
abstract: OBJECTIVE
  Classic serum tumor markers (human chorionic gonadotropin, α1-fetoprotein and lactate dehydrogenase) have an important role in managing testicular germ cell tumor. Since only 60% of all patients with testicular germ cell tumor have elevations of these markers, there is a need for new biomarkers with greater sensitivity/specificity. miRNAs are deregulated in cancer and could serve as noninvasive serum biomarkers. We explored the role of serum miRNAs as a novel biomarker in patients with testicular germ cell tumor.
  
  
  METHODS
  Total RNA was isolated from serum. miRNA levels were quantified by quantitative real-time polymerase chain reaction. We assessed the miRNAs miR-302a-3p, 302b-3p, 302c-3p, 367-3p, 371a-3p, 372-3p and 373-3p in a subcohort of 30 patients with testicular germ cell tumor and 18 healthy subjects. Validation was performed in 76 patients treated with inguinal exploration due to suspicion of testicular germ cell tumor, of whom 59 had cancer and 17 had benign disease, and in 84 healthy male subjects.
  
  
  RESULTS
  Serum miR-367-3p, 371a-3p, 372-3p and 373-3p levels were significantly increased in patients with testicular germ cell tumor compared to healthy individuals and patients with nonmalignant testicular disease. In particular miR-371a-3p allowed for sensitive (84.7%) and specific (99%) identification of patients with testicular germ cell tumor, thus, outperforming human chorionic gonadotropin or α1-fetoprotein testing. Furthermore, miR-367-3p was increased in nonseminoma compared to seminoma cases. Serum miRNA levels were increased in patients with advanced local stage and metastasis. In 9 patients with localized (clinical stage 1A) testicular germ cell tumor serum miR-371a-3p levels decreased postoperatively, indicating tumor specific release.
  
  
  CONCLUSIONS
  miR-371a-3p allows for better identification of testicular germ cell tumor than α1-fetoprotein and human chorionic gonadotropin. It could be helpful for clinically managing testicular germ cell tumor, especially for monitoring surveillance therapy and residual disease after chemotherapy.
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany. Electronic address: isabella.syring@ukb.uni-bonn.de.
authors.forename: Isabella
authors.initials: I
authors.lastname: Syring
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Bartels
authors.affiliation: Institut für Klinische Chemie und Klinische Pharmakologie, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Holdenrieder
authors.affiliation: Institut für Pathologie, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.affiliation: Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Bonn, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D009373:Neoplasms, Germ Cell and Embryonal / Q000097:blood* / Q000473:pathology; D013736:Testicular Neoplasms / Q000097:blood* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs
keywords: biological; microRNAs; serum; testicular germ cell tumor; testis; tumor markers