Identification and validation of a potential lung cancer serum biomarker detected by matrix-assisted laser desorption/ionization-time of flight spectra analysis
Identification and validation of a potential lung cancer serum biomarker detected by matrix-assisted laser desorption/ionization-time of flight spectra analysis
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DOI：
10.1002/pmic.200300514
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发表时间：
2003-09-01
期刊：
影响因子：
3.4
通讯作者：
Patz, EF
中科院分区：
文献类型：
--
作者：
Howard, BA;Wang, MZ;Patz, EF
常规影像学检查发现的胸部异常大多数是良性的，但由于担心可能发生癌症，所有这些异常都需要进一步评估。为了解决这一缺陷并开发肺癌的血清生物标志物，我们设计了一种基于基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）的平台，以显示存在于患有或不患有肺癌的患者血清中的蛋白质，然后挑战科学界分析这些数据，目的是确定所得光谱之间的特定离子信号差异。在m/z 11 702处发现了通过区分肺癌患者血清与非肺癌个体血清的各种分析算法鉴定的统计学上最显著的离子峰。我们通过部分纯化，然后通过凝胶内消化和肽图谱鉴定了负责该离子峰的蛋白质为血清淀粉样蛋白A（SAA; M-r = 11682.7）。通过酶联免疫吸附测定，我们发现SAA在癌症患者血清中的浓度为286 ng/mL，而在非癌症个体血清中的浓度为34.1 ng/mL。这些数据表明，MALDI-TOF MS和计算机分析的结合可以成为寻找肺癌和其他疾病的血清生物标志物的有力工具。
Many abnormalities detected in the thorax by routine conventional imaging studies are benign, yet all require further evaluation because of the concern for cancer. To address this deficiency and develop a serum biomarker for lung cancer, we designed a matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) based platform to display the proteins present in the serum of patients with or without lung cancer, and then challenged the scientific community to analyze these data with the aim of determining specific ion signal differences among the resulting spectra. The most statistically significant ion peak identified by the various analysis algorithms that differentiated the serum of patients with lung cancer from the serum of individuals without lung cancer was found at m/z 11 702. We identified the protein responsible for this ion peak as serum amyloid A (SAA; M-r = 11 682.7) by partial purification followed by in-gel digestion and peptide mapping. By enzyme-linked immunosorbent assay, we showed SAA to be present at 286 ng/mL in the serum of cancer patients vs. 34.1 ng/mL in the serum of individuals without cancer. These data suggest that the combination of MALDI-TOF MS and computer analysis can be a powerful tool in the search for serum biomarkers of lung cancer and other diseases.