title: MiR-200b and miR-155 as predictive biomarkers for the efficacy of chemoradiation in locally advanced head and neck squamous cell carcinoma.
abstract: The predictive value of microRNAs (miRNAs) in tumour cells and infiltrating immune cells for the efficacy of chemoradiation (CRTX) in locally advanced head and neck squamous cell carcinoma (HNSCC) was evaluated.
  
  
  
  Formalin-fixed, paraffin-embedded tumour material was collected from patients with locally advanced HNSCC treated within the ARO-0401 phase III trial with radiotherapy in combination with either 5-fluorouracil/cisplatin (CDDP-CRTX) or 5-fluorouracil/mitomycin C (MMC-CRTX). MiRNA and immune profiles were established in a test cohort of 48 oropharyngeal carcinoma (OPSCC) cases by Affymetrix miRNA microarrays and the nanoString PanCancer Immune Panel, respectively. Expression of miRNA candidates was measured in 149 HNSCC patients by real-time PCR. Interference of miRNA profiles with CRTX efficacy was determined by Kaplan-Meier and Cox regression analysis.
  
  
  
  Expression levels of five miRNAs (miR-27b, -130b, -200b, -451 and -532-5p) were significantly associated with overall survival after MMC-CRTX. Six different miRNAs (miR-125b, -146a, -150, -155, -187 and -342-5p) were correlated with overall survival after CDDP-CRTX. Validation by real-time PCR confirmed the predictive value of miR-200b and miR-155 in OPSCC, which was absent in hypopharyngeal carcinomas. MiR-146a was revealed as a prognostic marker for both CRTX regimens. MiR-200b expression was mainly associated with distant metastasis, whereas miR-155 correlated with local recurrence. MiR-155 and miR-146a were identified as surrogate markers for tumour-infiltrating lymphocytes.
  
  
  
  MiR-200b and miR-155 were established as potential markers for personalised treatment selection of two standard regimens of CRTX. The predictive role of miR-155 deserves further investigation, especially within the framework of clinical trials of CRTX/immune checkpoint inhibitor combinations.
authors.affiliation: Translational Radiooncology Research Laboratory, Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany.
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Hess
authors.affiliation: Translational Radiooncology Research Laboratory, Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany.
authors.forename: Annika
authors.initials: A
authors.lastname: Müer
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Fabian Dominik
authors.initials: FD
authors.lastname: Mairinger
authors.affiliation: Institute of Pathology, Technical University Munich, Munich, Germany.
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.affiliation: Institute of Pathology, Charité University Hospital, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Translational Radiooncology Research Laboratory, Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Budach
authors.affiliation: Translational Radiooncology Research Laboratory, Department of Radiooncology and Radiotherapy, Charité University Hospital, Berlin, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany; German Cancer Consortium (DKTK) Partner Site, Berlin, Germany. Electronic address: ingeborg.tinhofer@charite.de.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Tinhofer
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D059248:Chemoradiotherapy / Q000379:methods; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000235:genetics* / Q000628:therapy; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000502:physiology; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009959:Oropharyngeal Neoplasms / Q000235:genetics* / Q000628:therapy; D018579:Patient Selection; D057285:Precision Medicine / Q000379:methods; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; C533896:MIRN200 microRNA, human; D035683:MicroRNAs; D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil
keywords: Chemoradiotherapy; Gene expression signature; Head and neck cancer; Immune markers; Predictive biomarkers; Therapy outcome