骨髓增生异常综合征患者血清蛋白质组学特征研究  

Study on serum proteomic spectra in patients with myelodysplastic syndromes

作　　者：钟立业[1,2,3] 刘天浩[4] 李扬秋[3] 耿素霞[1,2] 陆泽生[1,2] 翁建宇[1,2] 吴穗晶[1,2,3] 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,广州市510080 [3]暨南大学医学院血液病研究所 [4]中山大学附属第二医院肿瘤科,广州市510120

出　　处：《实用医学杂志》2009年第21期3586-3588,共3页The Journal of Practical Medicine

基　　金：广东科技计划基金项目(编号:2006B36005009)

摘　　要：目的:利用铜螯合磁珠(magnetic beads-based immobilized metal affinity capture Cu)分离低峰度蛋白,以基质辅助激光解吸电离飞行时间质谱(matrix-assisted laser desorption/ionization time-of-flight mass spectrometry,MALDI-TOF-MS)技术分别检测骨髓增生异常综合征(myelodysplastic syndromes,MDS)患者和正常人血清蛋白质肽链的质量指纹谱,探索用于MDS辅助诊断的客观方法。方法:收集16例MDS患者(MDS组)和10例正常人(正常对照组)的血清蛋白标本,应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,并建立诊断模型。结果:分子质量1.02～10.25ku范围内共检测到信噪比>3的峰146个,经统计分析,MDS组和正常对照组之间差异明显,有显著性差异峰12个(P<0.05),利用快速分类算法建立诊断模型,模型的识别准确率和交叉验证敏感性分别达93.27%和89.94%。各亚型对比分析,各组间区域交叉,组间差异不明显;根据临床分型,将难治性贫血伴幼稚细胞增多型(RAEB型)与其他类型MDS比较,发现RAEB型患者血清中有1个差异低表达蛋白峰,分子质量约1466.57,经鉴定为纤维蛋白原N端片段。结论:MALDI-TOF-MS技术平台可用于寻找MDS相关的血清蛋白质标志物,其蛋白质谱诊断模型可以区分MDS与正常人,有助于MDS的临床辅助诊断。RAEB型患者与其他类型的MDS中存在差异表达蛋白,提示进展型MDS与其他类型MDS有异质性。Objective To investigate whether serum proteome profiling may serve as a noninvasive platform for establishing an objective models that may be beneficial to serologic diagnosis of myelodysplastic syndromes （MDS）. Methods Serum samples were collected from 16 patients with MDS and 10 healthy subjects. Serum peptides were separated and purified with a purification kit of magnetic beads-based immobilized metal affinity capture on the surface of superparamagnetic microparticles （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 MDS from healthy subjects, and diagnostic models were established by statistical analysis based on different expressed protein peaks. Results A total of 146 effective protein peaks were detected at molecular range from 1.02 to 10.25 ku, among which 12 protein peaks were different significantly between the MDS patients and the healthy subjects （P 〈 0.05）.The diagnostic models were established by rapid classification approach. The recognition capability and cross validation of the model were 93.27% and 89.94% respectively. However, there was not significant difference for peptide mass fingerprinting in patients with different subtypes of MDS. According to clinical classification of MDS, the protein peaks in RAEB compared with it in other subtypes of MDS, there was a significantly different expressed protein peak in 1 446.57 between them, which was identified as a piece of fibrinogen peptide. The expressions of fibrinogen in patients with RAEB were lower than patients with other subtypes of MDS. Conclusions MALDI-TOF-MS technique can help to identify serum proteomic biomarkers related to MDS. The diagnostic models can discriminate MDS patients from healthy subjects effectively and serve as a noninvasive diagnostic platform. The different expression of fibrinogen between RAEB and other subtypes suggested heterogeneity of etiopathogenisis betwee

关 键 词：骨髓增生异常综合征 蛋白质组学 血清 质谱 

分 类 号：R551.3[医药卫生—血液循环系统疾病]