利用MALDI-TOF-MS分析RAEB型骨髓增生异常综合征患者血清蛋白质组学特征  

Serum proteome in patients with RAEB myelodysplastic syndromes analyzed with MALDI-TOF-MS

作　　者：钟立业[1,2] 刘天浩[3] 耿素霞[1,2] 陆泽生[1,2] 翁建宇[1,2] 吴穗晶[1,2] 罗成伟[1,2] 杜欣[1,2] 

机构地区：[1]广东省医学科学院 [2]广东省人民医院肿瘤中心血液科,广东广州510080 [3]中山大学附属第二医院肿瘤科,广东广州510120

出　　处：《中华肿瘤防治杂志》2009年第21期1625-1628,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金："十一五"国家科技支撑计划项目(2008BAI61B02);广东科技计划基金项目(2006B36005009)

摘　　要：目的:利用铜螯合磁珠(MB-IMACCu)和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)技术,对比分析难治性贫血伴幼稚细胞增多型(RAEB)骨髓增生异常综合征(MDS)患者血清蛋白质谱特征,寻找差异表达蛋白,构建RAEB型MDS辅助诊断的血清蛋白质组学模型。方法:根据性别及年龄,配比收集RAEB型MDS、急性髓性白血病(AML)和正常人的血清蛋白标本各10例,利用铜螯合磁珠进行蛋白分离,通过MALDI-TOF-MS测定标本的蛋白质谱图,对比分析差异蛋白峰,并构建诊断模型。结果:与正常对照比较,在RAEB患者血清发现47个异常表达峰(P<0.05),其中高表达峰16个,低表达峰31个;以AML患者为疾病对照,获得33个异常表达峰(P<0.05),在RAEB中呈低表达的12个,呈高表达的21个。以基因遗传法构建诊断模型,结果提示,模型的识别准确率均达100%,敏感性达89.42%。结论:MB-IMACCu和MALDI-TOF-MS技术平台有助于RAEB型MDS相关的血清异常表达蛋白的研究,并且能够有效地区分RAEB患者、AML患者和正常人;根据血清差异蛋白质的组合峰所构建的诊断模型可辅助RAEB型MDS的诊断。OBJECTIVE：To investigate whether Magnetic Beads-based Immobilized Metal Affinity Capture Cu（MB-IMAC Cu）and serum proteome profiling may serve as a noninvasive platform to discover differently expressed proteins and establish the models that may help to serologic diagnosis of refractory anemia with excess blasts（RAEB）which is a subtype of myelodysplastic syndromes（MDS）.METHODS：Serum samples were collected from 10 RAEB patients and 10 acute myeloid leukemia patients and 10 age-and sex-matched healthy subjects.Serum peptides were separated and purified with a purification kit of MB-IMAC Cu.We generated serum proteome profiles by matrix-assisted laser desorption/ionization time·of-flight mass spectrometry（MALDI-TOF-MS）and identified a profile that distinguishes RAEB patients from AML patients and healthy subjects,and diagnostic models were established by statistical analysis based on differently expressed protein peaks.RESULTS：Forty-seven protein peaks were different significantly between RAEB patients and healthy subjects,of which 16 protein peaks were highly expressed and 31 protein peaks were weakly expressed in RAEB（P〈0.05）.Compared with AML,33 protein peaks were different significantly,of which 21 protein peaks were highly expressed and 12 protein peaks were weakly expressed in RAEB（P〈0.05）.The diagnostic models were established by genetic algorithm approach,and the recognition capabilities of the model were 100% and the rates of cross validation were 89.42% in Patients with RAEB.CONCLUSIONS：MALDI-TOF-MS technique can help to identify serum different proteins related to RAEB subtype MDS.The diagnostic models can discriminate RAEB patients from AML patients or healthy subjects effectively and help to identify RAEB clinical classification.

关 键 词：骨髓增生异常综合征 蛋白质组学 血蛋白质类/分析 

分 类 号：R551.3[医药卫生—血液循环系统疾病]