不同临床类型原发鼻咽癌组织差异表达蛋白

Differentially expressed proteins in the primary focus of nasopharyngeal carcinoma in different clinical types

目的寻找上行型、下行型和混合型不同临床类型鼻咽癌原发病瘤灶组织中的差异表达蛋白。方法采用双向凝胶电泳对不同临床类型鼻咽癌患者的鼻咽癌组织和正常人鼻咽组织总蛋白进行分离,对比找出差异表达蛋白质斑点,结合基质辅助激光解吸电离-飞行时间质谱分析技术和数据库信息检索鉴定差异蛋白点。结果与正常组比较,混合型鼻咽癌组出现31个差异蛋白质点,其中18个表达上调,13个表达下调;从混合型鼻咽癌组选择10个差异蛋白质斑点进行质谱鉴定,成功鉴定出5个,其中表达上调的有热休克固有蛋白、α1抗胰蛋白酶和巨噬细胞帽蛋白;表达下调的有S100A9蛋白和4.1蛋白。与下行型鼻咽癌组比较,上行型鼻咽癌组出现31个差异表达蛋白点,其中15个表达上调、16个表达下调;从上行型组选择10个差异蛋白质斑点进行质谱鉴定,成功鉴定出6个,其中表达上调的有线粒体顺乌头酸酶、乙醇脱氢酶、Rab GDP解离抑制因子β;表达下调的有NM23-H1、核氯离子通道蛋白27和乙醛脱氢酶X。结论不同临床类型鼻咽癌患者肿瘤转移相关蛋白、能量代谢蛋白、解毒蛋白与抗肿瘤转移蛋白表达水平存在差异,这些蛋白可作为临床分型标志物。

Objective To explore the differentially expressed protiens of the tumor tissues of nasopharyngeal carcinoma（NPC） primary focus in different clinical types including upward progressing type,downward progressing type and mixed progressing type.Methods The total proteins of tissues from normal nasopharyngeal mucosa and NPC in different clinical types were separated by two-dimensional electrophoresis（2-DE）,then proteins spots were analyzed and the differentially expressed proteins were identified by matrix assisted laser desorption/ionization time-offlight mass spectrometry（MALDI-TOF-MS） combined with bioinformatics analysis.Results Thirty-one significant differentially expressed proteins between mixed progressing type of NPC and normal tissues were found.Eighteen proteins were up-regulated and 13 proteins were down-regulated in mixed type of NPC.Five proteins of ten differential expressed proteins selected from mixed progressing type of NPC were identified by MALDI-TOF-MS.Heat shock cognate 71 kDa protein,alpha-1-antitrypsin and macrophage-capping protein were up-regulated and Protein S100A9 and Protein 4.1 were down-regulated in mixed progressing type of NPC.Thirty-one significant differentially expressed proteins between upward and downward progressing types of NPC were also found.And among of them,15 proteins were up-regulated and 16 proteins were down-regulated in upward progressing type of NPC as compared with those in downward progressing type of NPC.Six proteins of ten differential expressed proteins selected from upward progressing types of NPC were identified by MALDI-TOF-MS.Mitochondrial aconitate hydratase,alcohol dehydrogenase and Rab GDP dissociation inhibitor beta were up-regulated and NM23-H1,nuclear chloride channel-27 and aldehyde dehydrogenase X were down-regulated in upward progressing type of NPC as compared with those in downward progressing type of NPC.Conclusions There were significant differences at proteins related to tumor metastasis,energy metabolism,retoxity and anti-metastasis between different clinical type of NPC.These proteins may function as markers of clinical types of NPC.