Humphries Julia M, Penno Megan A S, Weiland Florian, Klingler-Hoffmann Manuela, Zuber Agnieszka, Boussioutas Alex, Ernst Matthias, Hoffmann Peter
Adelaide Proteomics Centre, School of Molecular Biomedical Science, The University of Adelaide, Adelaide, SA 5005, Australia.
Institute for Photonics & Advanced Sensing, The University of Adelaide, Adelaide, SA 5005, Australia.
Biochim Biophys Acta. 2014 May;1844(5):1051-8. doi: 10.1016/j.bbapap.2014.01.018. Epub 2014 Feb 7.
The timely detection of gastric cancer will contribute significantly towards effective treatment and is aided by the availability and reliability of appropriate biomarkers. A combination of several biomarkers can improve the sensitivity and specificity of cancer detection and this work reports results from a panel of 4 proteins. By combining a validated preclinical mouse model with a proteomic approach we have recently discovered novel biomarkers for the detection of gastric cancer. Here, we investigate the specificity of four of those biomarkers (afamin, clusterin, VDBP and haptoglobin) for the detection of gastric cancer using two independent methods of validation: ELISA, and a non antibody based method: Multiple Reaction Monitoring with High Resolution Mass Spectrometry (MRM-HR). All four biomarkers reliably differentiated GC from benign patient serum, and also in a small cohort of 11 early stage cases. We also present a novel isoform specific biomarker alpha-1-antitrypsin (A1AT) that was identified using a mouse model for gastric cancer. This isoform is distinct in charge and mobility in a pH gradient and was validated using human samples by isoelectric focussing and Western-blot (IEF-WB). This article is part of a Special Issue entitled: Biomarkers: A Proteomic Challenge.
胃癌的及时检测对有效治疗有显著贡献，合适生物标志物的可得性和可靠性对此有帮助。几种生物标志物的组合可提高癌症检测的灵敏度和特异性，本文报道了一组4种蛋白质的检测结果。通过将经过验证的临床前小鼠模型与蛋白质组学方法相结合，我们最近发现了用于检测胃癌的新型生物标志物。在此，我们使用两种独立的验证方法：酶联免疫吸附测定（ELISA）和一种基于非抗体的方法——高分辨率质谱多反应监测（MRM-HR），研究其中四种生物标志物（载脂蛋白A、簇集素、维生素D结合蛋白和触珠蛋白）在检测胃癌方面的特异性。所有这四种生物标志物都能可靠地将胃癌患者血清与良性患者血清区分开来，在一小群11例早期病例中也是如此。我们还展示了一种新的亚型特异性生物标志物α-1抗胰蛋白酶（A1AT），它是利用胃癌小鼠模型鉴定出来的。这种亚型在pH梯度中的电荷和迁移率不同，并通过等电聚焦和蛋白质免疫印迹（IEF-WB）使用人类样本进行了验证。本文是名为《生物标志物：蛋白质组学挑战》的特刊的一部分。
