Monitoring the serological proteome: The latest modality in prostate cancer detection
Monitoring the serological proteome: The latest modality in prostate cancer detection
复制标题
DOI：
10.1097/01.ju.0000132355.97888.50
复制
发表时间：
2004-07-01
影响因子：
6.6
通讯作者：
Ho, SM
中科院分区：
文献类型：
--
作者：
Mobley, JA;Lam, YW;Ho, SM
目的：最近出现了各种策略来提高前列腺癌（CaP）的诊断预测。一种这样的策略包括选择性地吸附到化学修饰的探针上的血清蛋白组分的质量分析。在目前的研究中，我们进一步验证了这种方法，同时提供了一个更通用的，更便宜的，但同样预测替代现有technology.Materials和Methods：一个固体核心亲脂性C-18树脂被用来提取和富集低分子量的蛋白质馏分从患者血清进一步分析质谱。使用多变量分析对从48名患者训练集产生的质谱进行数据挖掘，以鉴定诊断上显著的蛋白质峰。这些峰，然后被用来测试一个盲法研究组，包括168例患者与常见的统计算法和商业软件package.Results：共36个峰产生的训练集被用来测试的组合集的168个血清样本从98个健康人和70例CaP。我们报告的敏感性为94.1%，特异性为99.0%，1假阳性，4假阴性和5 nondiagnosed cases.Conclusions：我们的研究结果进一步表明，大量的血清学蛋白质谱提供了一种手段，为准确检测钙磷。此外，我们的方法被发现是上级的芯片为基础的协议，产生丰富的，尖锐的，高度可重复的光谱，可在高通量的方式和最低的成本。该技术也可用于使用多维蛋白质鉴定技术的后续蛋白质表征。最后，与商业上可用的统计应用的质谱分析被发现是非常有效的，在产生高度歧视的m/z值的CaP诊断。
Purpose: Various strategies have recently emerged to improve the diagnostic prediction of prostate cancer (CaP). One such strategy includes the mass profiling of serum protein fractions selectively adsorbed onto chemically modified probes. In the current study we further validated this approach, while offering a more versatile, less expensive and yet equally predictive alternative to existing technologies.Materials and Methods: A solid core lipophilic C-18 resin was used to extract and enrich the low molecular weight protein fraction from patient serum for further analysis by mass spectrometry. Mass spectra generated from a 48 patient training set were data mined using multivariate analysis to identify diagnostically significant protein peaks. These peaks were then used to test a blinded study set comprising 168 patients with common statistical algorithms and commercially available software packages.Results: A total of 36 peaks generated from the training set were used to test the combined set of 168 serum samples obtained from 98 healthy individuals and 70 patients with CaP. We report a sensitivity of 94.1% and a specificity of 99.0% with 1 false-positive, 4 false-negative and 5 nondiagnosed cases.Conclusions: Our results further indicate that mass profiling of serological proteins provides a means for the accurate detection of CaP. In addition, our approach was found to be superior to chip based protocols, generating rich, sharp, highly reproducible spectra attainable in a high throughput manner and at minimal cost. This technique is also scaleable for subsequent protein characterization using multidimensional protein identification technologies. Finally, analyses of mass spectra with commercially available statistical applications was found to be highly effective in generating highly discriminatory m/z values for CaP diagnosis.