Journal
ONCOTARGET
Volume 6, Issue 29, Pages 28478-28490Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4424
Keywords
nasopharyngeal carcinoma; xeroderma pigmentosum complementation group-A; platinum resistance; prognostic markers; chemoradiotherapy
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Funding
- National High Technology Research and Development Program of China (863 Program) [2012AA020803]
- National Basic Research Program of China (973 Program) [2012CB519003, 2011CB504304]
- National Natural Science Foundation of China [81071822, 81272638, 81472256]
- National Major Scientific and Technological Special Project [2012ZX09401015]
- Health & Medical Collaborative Innovation Project of Guangzhou City, China [201400000001]
- Guangdong Innovative Research Team Program [2009010058]
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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 IC50 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.
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