title: Circulating microRNAs as prognostic therapy biomarkers in head and neck cancer patients.
abstract: BACKGROUND
  The prediction of therapy response in head and neck squamous cell cancer (HNSCC) requires biomarkers, which are also a prerequisite for personalised therapy concepts. The current study aimed to identify therapy-responsive microRNAs (miRNAs) in the circulation that can serve as minimally invasive prognostic markers for HNSCC patients undergoing radiotherapy.
  
  
  METHODS
  We screened plasma miRNAs in a discovery cohort of HNSCC patients before therapy and after treatment. We further compared the plasma miRNAs of the patients to age- and sex-matched healthy controls. All miRNAs identified as biomarker candidates were then confirmed in an independent validation cohort of HNSCC patients and tested for correlation with the clinical outcome.
  
  
  RESULTS
  We identified a signature of eight plasma miRNAs that differentiated significantly (P=0.003) between HNSCC patients and healthy donors. MiR-186-5p demonstrated the highest sensitivity and specificity to classify HNSCC patients and healthy individuals. All therapy-responsive and patient-specific miRNAs in plasma were also detectable in tumour tissues derived from the same patients. High expression of miR-142-3p, miR-186-5p, miR-195-5p, miR-374b-5p and miR-574-3p in the plasma correlated with worse prognosis.
  
  
  CONCLUSIONS
  Circulating miR-142-3p, miR-186-5p, miR-195-5p, miR-374b-5p and miR-574-3p represent the most promising markers for prognosis and therapy monitoring in the plasma of HNSCC patients. We found strong evidence that the circulating therapy-responsive miRNAs are tumour related and were able to validate them in an independent cohort of HNSCC patients.
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Summerer
authors.affiliation: 1] Research Unit Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Unger
authors.affiliation: Research Unit Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Braselmann
authors.affiliation: 1] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Department of Radiation Oncology, Ludwig-Maximilians-Universitaet Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Schuettrumpf
authors.affiliation: 1] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Department of Radiation Oncology, Ludwig-Maximilians-Universitaet Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Maihoefer
authors.affiliation: 1] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-Universitaet Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Baumeister
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-Universitaet Muenchen, Thalkirchner Strasse 36, 80337 Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Kirchner
authors.affiliation: 1] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Department of Radiation Oncology, Ludwig-Maximilians-Universitaet Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Niyazi
authors.affiliation: Department of Radiation Oncology, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Sage
authors.affiliation: Department of Radiation Oncology, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich, Germany.
authors.forename: H M
authors.initials: HM
authors.lastname: Specht
authors.affiliation: 1] Department of Radiation Oncology, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich, Germany [2] Clinical Cooperation Group 'Innate Immunity', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Multhoff
authors.affiliation: Institute of Radiation Biology, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Moertl
authors.affiliation: 1] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Department of Radiation Oncology, Ludwig-Maximilians-Universitaet Muenchen, Marchioninistrasse 15, 81377 Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Belka
authors.affiliation: 1] Research Unit Radiation Cytogenetics, Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany [2] Clinical Cooperation Group 'Personalized Radiotherapy of Head and Neck Cancer', Helmholtz Center Munich, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Zitzelsberger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000628:therapy*; D015331:Cohort Studies; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs