title: XPF expression correlates with clinical outcome in squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Tumor-specific biomarkers that predict resistance to DNA damaging agents may improve therapeutic outcomes by guiding the selection of effective therapies and limiting morbidity related to ineffective approaches. XPF (ERCC4) is an essential component of several DNA repair pathways and XPF-deficient cells are exquisitely sensitive to DNA damaging agents. The purpose of this study was to determine whether XPF expression levels predict clinical response to DNA damaging agents in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Quantitative immunohistochemistry was used to measure XPF expression in tumors from a cohort of 80 patients with newly diagnosed HNSCC treated with radiation therapy with or without platinum-based chemotherapy; samples were collected prospectively. Genomic DNA isolated from blood samples was analyzed for nine single nucleotide polymorphisms (SNP) in the XPF gene by using a custom array. The primary endpoint was progression-free survival (PFS).
  
  
  RESULTS
  XPF expression was higher in tumors from the oral cavity than from the other sites (P < 0.01). High XPF expression correlated with early time to progression both by univariate (HR = 1.87, P = 0.03) and multivariate analysis (HR = 1.83, P = 0.05). The one year PFS for high expressers was 47% (95% CI = 31-62) compared with 72% (95% CI = 55-83) for low expressers. In addition, we identified four XPF SNPs that showed marginal association with treatment failure.
  
  
  CONCLUSIONS
  Expression level of XPF in HNSCC tumors correlates with clinical response to DNA damaging agents. XPF has potential to guide next generation personalized cancer therapy.
authors: Departments of Otolaryngology and Head and Neck Surgery, University of Pittsburgh School of Medicine and University of Pittsburgh Cancer Institute, PA 15213, USA. vaeziae@upmc.edu
authors: Alec
authors: A
authors: Vaezi
authors: Xiaozhe
authors: X
authors: Wang
authors: Shama
authors: S
authors: Buch
authors: William
authors: W
authors: Gooding
authors: Lin
authors: L
authors: Wang
authors: Raja R
authors: RR
authors: Seethala
authors: David T
authors: DT
authors: Weaver
authors: Alan D
authors: AD
authors: D'Andrea
authors: Athanassios
authors: A
authors: Argiris
authors: Marjorie
authors: M
authors: Romkes
authors: Laura J
authors: LJ
authors: Niedernhofer
authors: Jennifer R
authors: JR
authors: Grandis
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D002460:Cell Line; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D006801:Humans; D015151:Immunoblotting; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011878:Radiotherapy; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; C095888:xeroderma pigmentosum group F protein; D002945:Cisplatin