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基于磁珠的基质辅助激光解吸电离飞行时间质谱血清蛋白质谱分析检测肺腺癌。

Detection of lung adenocarcinoma using magnetic beads based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry serum protein profiling.

机构信息

Department of Respiratory Medicine, Second Affiliated Hospital of Medical College of Xi'an Jiao Tong University, Xi'an, Shaanxi 710004, China.

出版信息

Chin Med J (Engl). 2010 Jan 5;123(1):34-9.

Abstract

BACKGROUND

Recently, due to the rapid development of proteomic techniques, great advance has been made in many scientific fields. We aimed to use magnetic beads (liquid chip) based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) technology to screen distinctive biomarkers for lung adenocarcinoma (adCA), and to establish the diagnostic protein profiles.

METHODS

Using weak cation exchange magnetic beads (MB-WCX) to isolate and purify low molecular weight proteins from sera of 35 lung adCA, 46 benign lung diseases (BLDs) and 44 healthy individuals. The resulting spectra gained by anchor chip-MALDI-TOF-MS were analyzed by ClinProTools and a pattern recognition genetic algorithm (GA).

RESULTS

In the working mass range of 800 - 10 000 Da, 99 distinctive peaks were resolved in lung adCA versus BLDs, while 101 peaks were resolved in lung adCA versus healthy persons. The profile gained by GA that could distinguish adCA from BLDs was comprised of 4053.88, 4209.57 and 3883.33 Da with sensitivity of 80%, specificity of 93%, while that could separate adCA from healthy control was comprised of 2951.83 Da and 4209.73 Da with sensitivity of 94%, specificity of 95%. The sensitivity provided by carcinoembryonic antigen (CEA) in this experiment was significantly lower than our discriminatory profiles (P < 0.005). We further identified a eukaryotic peptide chain release factor GTP-binding subunit (eRF3b) (4209 Da) and a complement C3f (1865 Da) that may serve as candidate biomarkers for lung adCA.

CONCLUSION

Magnetic beads based MALDI-TOF-MS technology can rapidly and effectively screen distinctive proteins/polypeptides from sera of lung adCA patients and controls, which has potential value for establishing a new diagnostic method for lung adCA.

摘要

背景

近年来,由于蛋白质组学技术的快速发展,许多科学领域都取得了重大进展。我们旨在使用基于磁珠(液芯)的基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)技术筛选肺腺癌(adCA)的独特生物标志物,并建立诊断蛋白图谱。

方法

使用弱阳离子交换磁珠(MB-WCX)从 35 例肺腺癌、46 例良性肺部疾病(BLD)和 44 例健康个体的血清中分离和纯化低分子量蛋白。通过锚点芯片-MALDI-TOF-MS 获得的光谱由 ClinProTools 和模式识别遗传算法(GA)进行分析。

结果

在 800-10000 Da 的工作质量范围内,在肺腺癌与 BLDs 之间鉴定出 99 个独特峰,而在肺腺癌与健康个体之间鉴定出 101 个独特峰。GA 获得的能够区分 adCA 与 BLDs 的图谱由 4053.88、4209.57 和 3883.33 Da 组成,灵敏度为 80%,特异性为 93%,而能够区分 adCA 与健康对照的图谱由 2951.83 Da 和 4209.73 Da 组成,灵敏度为 94%,特异性为 95%。本实验中癌胚抗原(CEA)的灵敏度明显低于我们的鉴别谱(P<0.005)。我们进一步鉴定了一个真核肽链释放因子 GTP 结合亚基(eRF3b)(4209 Da)和一个补体 C3f(1865 Da),它们可能是肺腺癌的候选生物标志物。

结论

基于磁珠的 MALDI-TOF-MS 技术可以快速有效地从肺腺癌患者和对照者的血清中筛选出独特的蛋白质/多肽,这对于建立肺腺癌的新诊断方法具有潜在价值。

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