title: Nuclear expression of WRAP53β is associated with a positive response to radiotherapy and improved overall survival in patients with head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  Today there are no reliable predictive markers for radiotherapy response in head and neck squamous cell carcinoma (HNSCC), leading to both under- and over-treatment of patients, personal suffering, and negative socioeconomic effects. Inherited mutation in WRAP53β (WD40 encoding RNA Antisense to p53), a protein involved in intracellular trafficking, dramatically increases the risk of developing HNSCC. The purpose of this study was to investigate whether WRAP53β can predict response to radiotherapy in patients with HNSCC.
  
  
  METHODS
  Tumor biopsies from patients with HNSCC classified as responders or non-responders to radiotherapy were examined for the expression of the WRAP53β protein and single nucleotide polymorphisms in the corresponding gene employing immunohistochemistry and allelic discrimination, respectively. In addition, the effect of RNAi-mediated downregulation of WRAP53β on the intrinsic radiosensitivity of two HNSCC cell lines was assed using crystal violet and clonogenic assays.
  
  
  RESULTS
  Nuclear expression of WRAP53β was significantly associated with better response to radiotherapy and improved patient survival. Downregulation of WRAP53β with siRNA in vitro enhanced cellular resistance to radiation.
  
  
  CONCLUSIONS
  Our findings suggest that nuclear expression of WRAP53β promotes tumor cell death in response to radiotherapy and is a promising predictor of radiotherapy response in patients with HNSCC.
authors.affiliation: Department of Clinical Pathology and Clinical Genetics, and Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Garvin
authors.affiliation: Department of ENT - Head and Neck Surgery, County Council of Östergötland, Linköping, Sweden.
authors.forename: Katharina
authors.initials: K
authors.lastname: Tiefenböck
authors.affiliation: Department of ENT - Head and Neck Surgery, County Council of Östergötland, Linköping, Sweden.
authors.forename: Lovisa
authors.initials: L
authors.lastname: Farnebo
authors.affiliation: Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Lena K
authors.initials: LK
authors.lastname: Thunell
authors.affiliation: Department of Oncology - Pathology, Cancer Centrum Karolinska (CCK), Karolinska Institutet, Stockholm, Sweden.
authors.forename: Marianne
authors.initials: M
authors.lastname: Farnebo
authors.affiliation: Department of ENT - Head and Neck Surgery, County Council of Östergötland, Linköping, Sweden; Division of Oto-Rhino-Laryngology and Head and Neck Surgery, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden. Electronic address: karin.roberg@liu.se.
authors.forename: Karin
authors.initials: K
authors.lastname: Roberg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D001706:Biopsy; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D002467:Cell Nucleus / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000503:physiopathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D016019:Survival Analysis; D019098:Telomerase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018832:Molecular Chaperones; D019098:Telomerase; C535133:WRAP53 protein, human
keywords: Head and neck cancer; Predictive factors; Radiotherapy; Survivin; WRAP53