Identification of Biomarkers for Predicting Nasopharyngeal Carcinoma Response to Radiotherapy by Proteomics
Identification of Biomarkers for Predicting Nasopharyngeal Carcinoma Response to Radiotherapy by Proteomics
复制标题
通过蛋白质组学鉴定预测鼻咽癌放疗反应的生物标志物
DOI：
10.1158/0008-5472.can-09-4099
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发表时间：
2010-05-01
期刊：
影响因子：
11.2
通讯作者：
Xiao, Zhi-Qiang
中科院分区：
文献类型：
--
作者：
Feng, Xue-Ping;Yi, Hong;Xiao, Zhi-Qiang
放射治疗是鼻咽癌的主要治疗方法，但在许多病例中，放射抵抗仍然是成功治疗的严重障碍。为了鉴定与这种耐药有关的蛋白质，并评估它们预测鼻咽癌放射治疗反应的可能性，我们首先建立了由鼻咽癌细胞株CNE2经五轮亚致死电离辐射处理而来的放射抵抗亚克隆细胞系(CNE2-IR)。然后用蛋白质组学方法比较CNE2-IR和CNE2的蛋白质谱，共鉴定出34个差异蛋白质。其中14-3-3-Sigma和Maspin在辐射抗性CNE2-IR中表达下调，GRP78和Mn-SOD表达上调，经Western印迹证实。应用免疫组织化学方法检测39例放疗耐药和51例放疗敏感的鼻咽癌组织中4种有效蛋白的表达，并通过受试者工作特性分析评价其对鼻咽癌放射治疗疗效的预测价值。结果表明，14-3-3sigma和Maspin的表达下调以及GRP78和Mn-SOD的表达上调与鼻咽癌放射耐受密切相关，四种蛋白联合应用对鼻咽癌放射敏感性和特异性的敏感性和特异性分别为90%和88%。此外，CNE2-IR中14-3-3sigma的过度表达可以部分逆转对电离辐射的抗性。提示14-3-3 sigma、Maspin、GRP78和Mn-SOD是预测鼻咽癌放射治疗疗效的潜在生物标志物，它们的失调可能参与了鼻咽癌的放射抵抗。癌症资源；70(9)；3450-62。(C)2010年AACR。
Radiotherapy is the primary treatment for nasopharyngeal cancer (NPC), but radioresistance remains a serious obstacle to successful treatment in many cases. To identify the proteins involved in this resistance and to evaluate their potential for predicting NPC response to radiotherapy, we first established a radioresistant subclone cell line (CNE2-IR) derived from NPC cell line CNE2 by treating the cells with five rounds of sublethal ionizing radiation. Proteomics was then performed to compare the protein profiles of CNE2-IR and CNE2, and a total of 34 differential proteins were identified. Among them, 14-3-3 sigma and Maspin were downregulated and GRP78 and Mn-SOD were upregulated in the radioresistant CNE2-IR compared with control CNE2, which was conformed by Western blot. Immunohistochemistry was performed to detect the expression of the four validated proteins in the 39 radioresistant and 51 radiosensitive NPC tissues and their value for predicting NPC response to radiotherapy were evaluated by receiver operating characteristic analysis. The results showed that the downregulation of 14-3-3 sigma and Maspin and the upregulation of GRP78 and Mn-SOD were significantly correlated with NPC radioresistance and the combination of the four proteins achieved a sensitivity of 90% and a specificity of 88% in discriminating radiosensitive from radiaoresistant NPC. Furthermore, the resistance to ionizing radiation can be partially reversed by the overexpression of 14-3-3 sigma in the CNE2-IR. The data suggest that 14-3-3 sigma, Maspin, GRP78, and Mn-SOD are potential biomarkers for predicting NPC response to radiotherapy and their dysregulation may be involved in the radioresistance of NPC. Cancer Res; 70(9); 3450-62. (C) 2010 AACR.