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应用磁珠联合MALDI-TOF MS技术建立前列腺癌血清差异蛋白诊断模型

董德鑫,  李汉忠,  严维刚,  纪志刚,  毛全宗

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文章导航 > 协和医学杂志  > 2012 >  3(4): 437-440
董德鑫, 李汉忠, 严维刚, 纪志刚, 毛全宗. 应用磁珠联合MALDI-TOF MS技术建立前列腺癌血清差异蛋白诊断模型[J]. 协和医学杂志, 2012, 3(4): 437-440. doi: 10.3969/j.issn.1674-9081.2012.04.017
引用本文: 董德鑫, 李汉忠, 严维刚, 纪志刚, 毛全宗. 应用磁珠联合MALDI-TOF MS技术建立前列腺癌血清差异蛋白诊断模型[J]. 协和医学杂志, 2012, 3(4): 437-440. doi: 10.3969/j.issn.1674-9081.2012.04.017
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De-xin DONG, Han-zhong LI, Wei-gang YAN, Zhi-gang JI, Quan-zong MAO. Application of Weak Cation Exchange Magnetic Beads Combined MALDI-TOF MS in Detecting Differentially Expressed Proteins in Serum of Prostate Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(4): 437-440. doi: 10.3969/j.issn.1674-9081.2012.04.017
Citation: De-xin DONG, Han-zhong LI, Wei-gang YAN, Zhi-gang JI, Quan-zong MAO. Application of Weak Cation Exchange Magnetic Beads Combined MALDI-TOF MS in Detecting Differentially Expressed Proteins in Serum of Prostate Cancer[J]. Medical Journal of Peking Union Medical College Hospital, 2012, 3(4): 437-440. doi: 10.3969/j.issn.1674-9081.2012.04.017
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应用磁珠联合MALDI-TOF MS技术建立前列腺癌血清差异蛋白诊断模型

doi: 10.3969/j.issn.1674-9081.2012.04.017

  • 中国医学科学院 北京协和医学院 北京协和医院泌尿外科, 北京 100730

基金项目: 

国家自然科学基金 30772165

详细信息
    通讯作者:

    李汉忠 电话:010-69156073, E-mail:winterheart@163.com

  • 中图分类号: R737.25

Application of Weak Cation Exchange Magnetic Beads Combined MALDI-TOF MS in Detecting Differentially Expressed Proteins in Serum of Prostate Cancer

  • Department of Urology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China

More Information

    摘要
  • 摘要:   目的  应用蛋白组学技术对前列腺癌血清差异蛋白进行筛选, 并建立前列腺癌诊断模型。  方法  2010年3月至5月间于北京协和医院泌尿外科病房采集12例前列腺癌患者及11例非前列腺癌对照者血清样本, 应用弱阳离子磁珠联合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)技术对前列腺癌患者和对照者血清进行差异蛋白研究, 筛选出多个前列腺癌血清差异蛋白, 并应用ClinProTools 2.2软件通过遗传算法建立诊断模型。  结果  共筛选出前列腺癌与对照组之间差异蛋白峰126个, 具有较明显差异的蛋白峰24个(P=0.178)。通过遗传算法优化选择, 筛选出符合条件的15个差异蛋白峰建立诊断模型, 交叉验证准确性为81.82%, 识别能力为100%。  结论  应用磁珠联合MALDI-TOF MS技术及遗传算法成功建立前列腺癌血清差异蛋白的诊断模型, 该模型识别能力高, 有助于减少前列腺癌的漏诊率。
    Abstract:   Objective  To detect differentially expressed proteins in serum of prostate cancer and to establish a diagnostic model for prostate cancer.  Methods  Serum samples from 12 patients with prostate cancer and 11 controls hospitalized at our department from March to May 2010 were collected. The weak cation exchange (WCX) beads combined matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) technique was used to detect the differentially expressed proteins in the serum samples of prostate cancer patients and controls. Differentially expressed proteins for prostate cancer were then screened out. Genetic algorithm was utilized to establish a diagnostic model for prostate cancer with ClinProTools 2.2 software.  Results  Totally 126 different proteins were screened out, of which 24 were significantly different between the prostate cancer patients and controls (P=0.178). Using the genetic algorithm, 15 differentially expressed proteins were screened out to establish a diagnostic model. The cross-validation of the model was 81.82% and the recognition rate was 100%.  Conclusions  A diagnostic model of prostate cancer using the WCX magnetic beads combined MALDI-TOF MS technique and genetic algorithm was successfully established. This model has high cross-validation and recognition rate and is helpful to reduce the misdiagnosis rate of prostate cancer.
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  • 图  1  标准品质谱图谱

    下载: 全尺寸图片 幻灯片

    图  2  前列腺癌组(绿色)与对照组(红色)样本之间血清差异蛋白峰

    下载: 全尺寸图片 幻灯片

    图  3  前列腺癌组(绿色)与对照组(红色)样本血清差异蛋白峰凝胶模拟示意图

    下载: 全尺寸图片 幻灯片

    表  1  筛选出符合条件的15个差异蛋白峰建立前列腺癌诊断模型

    编号 相对分子质量 起始相对分子质量 结束相对分子质量 权重
    57 2903. 16 2897. 61 2910. 48 0. 8680560448445466
    79 3958. 66 3944. 72 3969. 57 0. 1679614918991689
    100 5340. 17 5325. 84 5362. 8 0. 04823311872036732
    47 2562. 87 2559. 19 2574. 54 0. 849189370352345
    49 2633. 03 2630. 74 2635. 92 0. 5328721108794765
    69 3311. 45 3300. 23 3313. 96 0. 5130303457949107
    14 1331. 39 1328. 92 1336. 63 0. 09335411780632828
    86 4213. 08 4200. 89 4231. 91 0. 1625069730481389
    96 5135. 93 5116. 02 5144. 98 0. 1998079658204655
    70 3317. 88 3313. 96 3329. 84 0. 7422365028263824
    111 6437. 68 6420. 03 6463. 56 0. 4634096271299009
    113 6635. 89 6609. 25 6659. 42 0. 6268605478105982
    41 2273. 97 2267. 09 2278. 47 0. 4187220238328942
    99 5268. 31 5261. 65 5277. 66 0. 6419938624386253
    58 2934. 76 2920. 89 2940. 78 0. 7053164233366787
    下载: 导出CSV
    • 参考文献(9)
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    [2] Kumarathasan P, Mohottalage S, Goegan P, et al. An optimized protein in-gel digest method for reliable proteome characterization by MALDI-TOF-MS analysis[J]. Anal Biochem, 2005, 346:85-89. doi:  10.1016/j.ab.2005.06.004
    [3] Adam BL, Qu Y, Davis JW, et al. Serum protein fingerprinting coupled with a pattern-matching algorithm distinguishes prostate cancer from benign prostate hyperplasia and healthy men[J]. Cancer Res, 2002, 62:3609-3614.
    [4] Bailey SJ, Brewster SF. Prostate cancer:to screen or not to screen[J]. Arch Esp Urol, 2011, 64:406-418.
    [5] 周毅, 李汉忠, 严维刚.模板定位下经会阴前列腺分区穿刺活检1270例临床研究[J].中华泌尿外科杂志, 2010, 31:395-398. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zhmnwk201006009
    [6] Wong MY, Yu KO, Poon TC, et al. A magnetic bead-based serum proteomic fingerprinting method for parallel analytical analysis and micropreparative purification[J]. Electrophoresis, 2010, 31:1721-1730. doi:  10.1002/elps.200900571
    [7] Giebel R, Worden C, Rust SM, et al. Microbial fingerprinting using matrix-assisted laser desorption ionization time-offlight mass spectrometry (MALDI-TOF MS) applications and challenges[J]. Adv Appl Microbiol, 2010, 71:149-184. doi:  10.1016/S0065-2164(10)71006-6
    [8] Fung ET, Wright GL Jr, Dalmasso EA. Proteomic strategies for biomarker identification:progress and challenges[J]. Curr Opin Mol Ther, 2000, 2:643-650.
    [9] 李绍新, 张延娇.标准遗传算法引入遗传策略和突变算子对蛋白质2D折叠模拟的影响[J].广东医学院学报, 2008, 26:499-502. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=gdyxyxb200805004
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出版历程
  • 收稿日期:  2011-07-11
  • 刊出日期:  2012-10-30

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