Cheng Ai-Lan, Huang Wei-Guo, Chen Zhu-Chu, Peng Fang, Zhang Peng-Fei, Li Mao-Yu, Li Feng, Li Jian-Ling, Li Cui, Yi Hong, Yi Bin, Xiao Zhi-Qiang
Key Laboratory of Cancer Proteomics of Chinese Ministry of Health and Medical Research Center, Xiangya Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China.
Clin Cancer Res. 2008 Jan 15;14(2):435-45. doi: 10.1158/1078-0432.CCR-07-1215.
To identify novel nasopharyngeal carcinoma (NPC) biomarkers by laser capture microdissection and a proteomic approach.
Proteins from pooled microdissected NPC and normal nasopharyngeal epithelial tissues (NNET) were separated by two-dimensional gel electrophoresis, and differential proteins were identified by mass spectrometry. Expression of three differential proteins (stathmin, 14-3-3sigma, and annexin I) in the above two tissues as well as four NPC cell lines was determined by Western blotting. Immunohistochemistry was also done to detect the expression of three differential proteins in 98 cases of primary NPC, 30 cases of NNET, and 20 cases of cervical lymph node metastases, and the correlation of their expression levels with clinicopathologic features and clinical outcomes were evaluated.
Thirty-six differential proteins between the NPC and NNET were identified. The expression levels of stathmin, 14-3-3sigma, and annexin I in the two types of tissues were confirmed and related to differentiation degree and/or metastatic potential of the NPC cell lines. Significant stathmin up-regulation and down-regulation of 14-3-3sigma and annexin I were observed in NPC versus NNET, and significant down-regulation of 14-3-3sigma and annexin I was also observed in lymph node metastasis versus primary NPC. In addition, stathmin up-regulation and down-regulation of 14-3-3sigma and annexin I were significantly correlated with poor histologic differentiation, advanced clinical stage, and recurrence, whereas down-regulation of 14-3-3sigma and annexin I was also significantly correlated with lymph node and distant metastasis. Furthermore, survival curves showed that patients with stathmin up-regulation and down-regulation of 14-3-3sigma and annexin I had a poor prognosis. Multivariate analysis revealed that the expression status of stathmin, 14-3-3sigma, and annexin I was an independent prognostic indicator.
The data suggest that stathmin, 14-3-3sigma, and annexin I are potential biomarkers for the differentiation and prognosis of NPC, and their dysregulation might play an important role in the pathogenesis of NPC.
通过激光捕获显微切割和蛋白质组学方法鉴定新的鼻咽癌（NPC）生物标志物。
通过二维凝胶电泳分离来自汇集的显微切割NPC和正常鼻咽上皮组织（NNET）的蛋白质，并用质谱法鉴定差异蛋白。通过蛋白质印迹法测定上述两种组织以及四种NPC细胞系中三种差异蛋白（微管蛋白、14-3-3σ和膜联蛋白I）的表达。还进行了免疫组织化学检测98例原发性NPC、30例NNET和20例颈部淋巴结转移中三种差异蛋白的表达，并评估其表达水平与临床病理特征和临床结局的相关性。
鉴定出NPC和NNET之间的36种差异蛋白。证实了两种组织中微管蛋白、14-3-3σ和膜联蛋白I的表达水平，并与NPC细胞系的分化程度和/或转移潜能相关。与NNET相比，NPC中观察到微管蛋白显著上调，14-3-3σ和膜联蛋白I显著下调；与原发性NPC相比，淋巴结转移中也观察到14-3-3σ和膜联蛋白I显著下调。此外，微管蛋白上调以及14-3-3σ和膜联蛋白I下调与组织学分化差、临床分期晚和复发显著相关，而14-3-3σ和膜联蛋白I下调也与淋巴结和远处转移显著相关。此外，生存曲线显示微管蛋白上调以及14-3-3σ和膜联蛋白I下调的患者预后较差。多变量分析显示微管蛋白、14-3-3σ和膜联蛋白I的表达状态是独立的预后指标。
数据表明微管蛋白, 14-3-3σ和膜联蛋白I是NPC分化和预后的潜在生物标志物，它们的失调可能在NPC发病机制中起重要作用。
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