Identification of candidate biomarkers for the early detection of nasopharyngeal carcinoma by quantitative proteomic analysis
Identification of candidate biomarkers for the early detection of nasopharyngeal carcinoma by quantitative proteomic analysis
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通过定量蛋白质组分析鉴定鼻咽癌早期检测的候选生物标志物
DOI：
10.1016/j.jprot.2014.06.025
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发表时间：
2014-09-23
影响因子：
3.3
通讯作者：
Li，Guiyuan
中科院分区：
文献类型：
--
作者：
Yang，Jing;Zhou，Ming;Li，Guiyuan
鼻咽癌是一种主要的头颈部肿瘤，在东南亚和中国南部高发。为了寻找新的鼻咽癌患者早期诊断的生物标志物，采用2D-DGE结合MALDI-TOF-MS分析方法，从LCM纯化的正常鼻咽上皮组织和不同阶段的鼻咽癌活检组织中筛选出在鼻咽癌发生发展过程中差异表达的蛋白质。结果鉴定出26个差异表达的蛋白质，其中两个在致癌过程中表达急剧变化的蛋白质ENO1和CyPA经蛋白质印迹分析证实是功能网络中的关键种子蛋白质。免疫组织化学方法检测不同分期鼻咽癌组织中两种蛋白的表达。通过接收器工作特性分析评估这些蛋白质早期检测鼻咽癌的能力。结果表明，两种蛋白联合应用能较好地区分NNET和AH与鼻咽癌I期，具有较高的敏感性和特异性，比单独使用两种蛋白单独使用更有效。综上所述，ENO1和CyPA联合检测可作为早期发现鼻咽癌的潜在分子标志物。生物学意义鼻咽癌是东南亚最常见的致命性恶性肿瘤，早期发现和治疗对鼻咽癌患者的生存和预后至关重要。在本工作中，我们利用2D-DGE结合MALDI-TOF/TOF分析，鉴定了26个在NNET、AH和不同分期的鼻咽癌组织中差异表达的蛋白质。其中，ENO1的下调和CyPA的过度表达被高通量的组织芯片证实，该芯片包括不同阶段的鼻咽癌组织，结果表明ENO1和CyPA的结合可以作为鼻咽癌早期检测的潜在分子标志物。
Nasopharyngeal carcinoma (NPC) is a major head and neck cancer with high occurrence in Southeast Asia and southern China. To identify novel biomarkers for the early detection of NPC patients, 2D-DIGE combined with MALDI-TOF-MS analysis was performed to identify differentially expressed proteins in the carcinogenesis and progression of NPC using LCM-purified normal nasopharyngeal epithelial tissues and various stages of NPC biopsies. As a result, 26 differentially expressed proteins were identified, of which two proteins with sharp expressional changes in the carcinogenic process, ENO1 and CYPA, were validated by western blot analysis and identified as critical seed proteins in the functional network. Immunohistochemistry assay was further performed to detect the expression of the two proteins with a tissue microarray that included various stages of NPC tissues. The ability of these proteins to detect NPC early was evaluated via a receiver operating characteristic analysis. The results indicated that the combination of the two proteins could perfectly discriminate NNET and AH from stage I of NPC with high sensitivity and specificity, which is more effective than using either of the two proteins individually. In summary, the combination of ENO1 and CYPA can serve as potential molecular markers for the early detection of NPC.Biological significanceNPC is a lethal malignancy that is most prevalent in Southeast Asia, and early detection and treatment are essential for the survival and good prognosis of NPC patients. In the present work, we identified 26 differentially expressed proteins in NNET, AH and different stages of NPC tissues by using 2D-DIGE combined with MALDI-TOF/TOF analysis. Of these proteins, the down-regulation of ENO1 and over-expression of CYPA were confirmed with a high-throughput tissue microarray that included various stages of NPC tissues via an IHC assay, and the results indicated that the combination of ENO1 and CYPA can serve as a potential molecular marker for the early detection of NPC.