High expression of XPA confers poor prognosis for nasopharyngeal carcinoma patients treated with platinum-based chemoradiotherapy

// Xiang Fu 1,2,* , Jiali Hu 1,* , Hong-yu Han 1,* , Yi-jun Hua 1,* , Ling Zhou 1 , Wen-di Shuai 1 , Wu-ying Du 1 , Chun-mei Kuang 1 , Shuai Chen 1 , Wenlin Huang 1,3 and Ran-yi Liu 1 1 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China 2 The Eastern Hospital of the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China 3 Guangdong Provincial Key Laboratory of Tumor targeted Drugs and Guangzhou Enterprise Key Laboratory of Gene Medicine, Guangzhou Doublle Bioproducts Co. Ltd., Guangzhou, China * These authors have contributed equally in this work Correspondence to: Ran-yi Liu, email: // Wenlin Huang, email: // Keywords : nasopharyngeal carcinoma, xeroderma pigmentosum complementation group-A, platinum resistance, prognostic markers, chemoradiotherapy Received : March 30, 2015 Accepted : June 04, 2015 Published : June 10, 2015 Abstract In this study, we tried to explore if xeroderma pigmentosum complementation group-A (XPA) expression is likely a prognostic prediction factor for locally advanced nasopharyngeal carcinoma (NPC) patients treated with platinum-based chemoradiotherapy, which was considered to bring chemotherapy-related severe toxicity compared with radiotherapy alone. Firstly, MTT assay revealed that downregulating XPA expression in NPC HONE1 and CNE1 cells decreased IC 50 of cisplatin and sensitized cells to cisplatin. XPA expression was detected by immunohistochemistry in cancer tissues from locally advanced NPC patients treated with platinum-based chemoradiotherapy. The relationships between XPA expression and clinicopathologic features, overall survival and progression-free survival of patients were evaluated. The results showed that XPA expression was not associated with clinicopathologic parameters, but was likely an independent prognostic factor for patient survival. High XPA level predicts a poor prognosis, and the prediction values were higher in subgroups of younger, higher EBV antibody titer, or treated with concurrent chemoradiotherapy. Combining XPA levels and T/N classifications, we successfully classified these patients into low, medium and high risk groups for platinum-based chemoradiotherapy. These findings suggest that XPA levels may be a potential predictor of prognosis in locally advanced NPC patients treated with platinum-based chemoradiotherapy, and helpful for selecting patients likely to need and benefit from this treatment in future.