XPF expression correlates with clinical outcome in squamous cell carcinoma of the head and neck by Vaezi Alec, Wang Xiaozhe, Buch Shama C, Gooding William E, Wang Lin, Seethala Raja R, Weaver David, D'Andrea Alan D, Argiris Athanassios, Marjorie Romkes, Niedernhofer Laura J, Grandis Jennifer R in Clinical cancer research : an official journal of the American Association for Cancer Research (2011). PubMed

Abstract

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 in the XPF gene 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 to 72% (95% CI = 55% - 83%) for low expressers. In addition, we identified four XPF single nucleotide polymorphisms (SNPs) that demonstrated 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.

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