title: A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy.
  
  
  METHODS
  We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray.
  
  
  RESULTS
  In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) (p=0.02), Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2 (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03) and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased.
  
  
  CONCLUSIONS
  All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.
authors: Department of Otolaryngology, Head and Neck Surgery, Surgical Services, Oakland University - William Beaumont School of Medicine, Royal Oak, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden. Electronic address: jan.akervall@beaumont.edu.
authors: Jan
authors: J
authors: Akervall
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.
authors: Sirisha
authors: S
authors: Nandalur
authors: Van Andel Institute, Grand Rapids, MI, USA.
authors: Jacob
authors: J
authors: Zhang
authors: Van Andel Institute, Grand Rapids, MI, USA.
authors: Chao-Nan
authors: CN
authors: Qian
authors: Department of Pathology, William Beaumont Hospital, Royal Oak, MI, USA.
authors: Neal
authors: N
authors: Goldstein
authors: Van Andel Institute, Grand Rapids, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
authors: Paulina
authors: P
authors: Gyllerup
authors: Van Andel Institute, Grand Rapids, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
authors: Ylva
authors: Y
authors: Gardinger
authors: Van Andel Institute, Grand Rapids, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
authors: Jens
authors: J
authors: Alm
authors: Van Andel Institute, Grand Rapids, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
authors: Katarina
authors: K
authors: Lorenc
authors: Van Andel Institute, Grand Rapids, MI, USA; Department of Otolaryngology, Head and Neck Surgery, University Hospital, Lund, Sweden.
authors: Karolina
authors: K
authors: Nilsson
authors: Van Andel Institute, Grand Rapids, MI, USA.
authors: James
authors: J
authors: Resau
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, USA.
authors: George
authors: G
authors: Wilson
authors: Van Andel Institute, Grand Rapids, MI, USA.
authors: Bin
authors: B
authors: Teh
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D005260:Female; D020869:Gene Expression Profiling; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D011836:Radiation Tolerance; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D014408:Biomarkers, Tumor
keywords: Head and neck cancer; Predictive biomarkers; Radio-resistance; Squamous cell carcinoma; YAP-1; c-MET