Abstract 4727: Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients

Abstract

Abstract Background: DNA repair genes function in the maintenance of genome integrity and prevent tumorigenesis. On another hand, DNA repair genes modulate cancer cell responses to DNA-damaging therapeutics. We hypothesize that altered expression of DNA repair genes are correlated with therapeutic outcomes of head and neck cancer patients. Patients and methods: Messenger RNA (mRNA) expressions of DDB2 and XPC were examined in specimens of 95 head and neck cancer patients using real-time quantitative RT-PCR. Patients were dichotomized by ROC curve analysis based on their DDB2 and XPC mRNA levels. Overall survival (OS) rates were measured using Kaplan-Meier estimates and the log-rank tests. The adjusted hazard rate ratios (HRRs) were computed by multivariate Cox regressions. Results: The levels of DDB2 and XPC mRNA expression in tumor tissues were reduced (tumor/normal < 0.9) in 84 and 80 cases, respectively, when compared with those in adjacent normal parts. Lower DDB2 (tumor/normal < 0.24) and XPC (tumor/normal < 0.36) mRNA expressions were correlated with larger tumor, positive lymph node invasion, advanced stage, and poor 5-yr OS rates (26.7% vs. 54.3%, and 28.1% vs. 53.0%, respectively). Multivariate Cox model showed that, in addition to T and N stages, lower XPC mRNA level (< 0.36) was an independent risk factor for patient's survival (HRR = 2.68, 95% CI 1.12-6.40). Concurrent chemotherapy and radiotherapy (CCRT) did not improve OS of patients with lower XPC mRNA (< 0.36) and showed even worse outcomes within 5 years for patients with lower DDB2 expression (< 0.24). However, patients with higher DDB2 (> 0.24) and XPC (> 0.36) mRNA levels had improved 5-yr OS rates if they received CCRT (64.4% vs. 41.8% and 73.3% vs. 39.2%). Conclusion: mRNA expressions of XPC and DDB2 might be useful biomarkers for prognosis and efficacy of CCRT medication in head and neck cancer patients. Citation Format: Chang-Shen Lin, Ka-Wo Lee, Jau-Ling Huang, Yu-Chu Wang, Yi-Shan Tsai. Prognostic roles of DDB2 and XPC mRNA expressions in treatment responses and overall survivals of head and neck cancer patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4727. doi:10.1158/1538-7445.AM2014-4727