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Updated: May 31, 2026
Establishment of a Clinic-based Biorepository
Published on: May 29, 2017
XPF expression correlates with clinical outcome in squamous cell carcinoma of the head and neck
Alec Vaezi1, Xiaozhe Wang, Shama Buch
1Departments 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
Purpose:
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).
Experimental Design:
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.
Insights
XPF expression levels in head and neck squamous cell carcinoma (HNSCC) predict response to DNA damaging agents. High XPF expression correlates with poorer progression-free survival, indicating its potential for personalized cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Tumor biomarkers predicting resistance to DNA damaging agents can optimize cancer therapy.
- XPF (ERCC4) is crucial for DNA repair, and its deficiency increases sensitivity to DNA damaging agents.
Purpose of the Study:
- To investigate if XPF expression levels predict clinical response to DNA damaging agents in head and neck squamous cell carcinoma (HNSCC).
Main Methods:
- Quantitative immunohistochemistry measured XPF expression in 80 HNSCC patients treated with radiation and/or platinum chemotherapy.
- XPF gene single nucleotide polymorphisms (SNPs) were analyzed.
- Progression-free survival (PFS) was the primary endpoint.
Main Results:
- Higher XPF expression was observed in oral cavity tumors (P < 0.01).
- High XPF expression correlated with shorter time to progression (univariate HR=1.87, P=0.03; multivariate HR=1.83, P=0.05).
- One-year PFS was 47% for high XPF expressers versus 72% for low expressers. Four XPF SNPs showed marginal association with treatment failure.
Conclusions:
- XPF expression levels in HNSCC tumors correlate with clinical response to DNA damaging agents.
- XPF has potential as a biomarker to guide personalized cancer therapy.
