人脑星形胶质细胞瘤恶性程度相关蛋白表达谱的分析与鉴定

Proteomic profiling and identification of malignant grade related proteins in human brain astrocytoma

目的应用蛋白质组学技术确定与人脑星形胶质细胞瘤恶性程度相关的差异表达蛋白质分子。方法二维电泳技术比较分析12例正常脑组织和52例不同恶性程度星形胶质细胞瘤组织（Ⅱ级23例、Ⅲ级15例、Ⅳ级14例）差异表达蛋白质斑点，高效液相色谱-电喷雾（ESI）串联质谱技术、生物信息学方法分析鉴定与恶性程度相关的差异表达蛋白质分子。结果共鉴定出15种差异表达的蛋白质分子，其中热休克蛋白27、抑制素、葡萄糖调节蛋白78、过氧化物氧化酶1、过氧化物氧化酶6、膜联蛋白Ⅱ、组织蛋白酶D、纤溶酶原激活物抑制剂-1、肌动蛋白（胞浆型1）、谷胱甘肽S-转移酶M这10种蛋白的表达在Ⅲ级和Ⅳ级星形胶质细胞瘤组织中升高，二硫键异构酶A3、αB晶体蛋白质、T复合体蛋白1（ε亚单位1、泛素C-末端水解酶同工酶L1、胶质纤维酸性蛋白这5种蛋白的表达降低。结论蛋白质组学技术可有效鉴定与肿瘤恶性程度相关的差异表达蛋白，为星形胶质细胞瘤的分子个体诊断和分子靶向治疗提供实验依据。

Objective To determine the malignant grade related proteins implicated in human astrocytoma with proteomic techniques. Methods Two-dimensional electrophoresis （2-DE） was used to compare the protein expression profiles of normal human brain tissues （n=12） and astrocytoma tissue samples of various malignant grades （23 with grade II, 15 with grade III and 14 with grade IV）. After identifying the differential protein spots, electrospray ionization （ESI） tandem mass spectrum and bioinformatics were employed to determine the protein 1D. Results A total of 15 proteins with differential expressions were identified, which included 10 up-regulated ones （heat shock protein 27, prohibitin, 78-kDa glucose-regulated protein, peroxiredoxin 1, peroxiredoxin 6, annexin II, eathepsin D, plasminogen activator inhibitor-l, actin [cytoplasmic 1], Glutathione S-transferase M） and 5 down-regulated proteins （disulfide isomerase A3 protein, alpha-crystallin B chain protein, T-complex protein 1 e subunit, ubiquitin carboxyl-terminal hydrolase isozyme L1 and glial fibrillary acidic protein） in astrocytoma tissues of grade III and IV. Conclusion Proteomic techniques can screen the malignant-grade associated proteins effectively, which provides rationale for individualized diagnosis and therapeutic targets of astrocytoma.