Multicenter Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) Identifies Proteomic Differences in Breast-Cancer-Associated Stroma
Multicenter Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI MSI) Identifies Proteomic Differences in Breast-Cancer-Associated Stroma
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DOI：
10.1021/pr500253j
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发表时间：
2014-11-01
影响因子：
4.4
通讯作者：
McDonnell, Liam A.
中科院分区：
文献类型：
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作者：
Dekker, Tim J. A.;Balluff, Benjamin D.;McDonnell, Liam A.
MALDI质谱成像（MSI）已迅速成为一种强大的生物标志物发现工具。到目前为止，还没有正式的调查评估中心间的可比性MALDI MSI实验，它发展成为一种新的诊断方法的必要步骤。为了测试这种能力，我们进行了一项多中心研究，重点关注乳腺癌基质激活的生物标志物。MALDI MSI实验在两个中心使用独立的组织库、基础设施、方法和从业人员进行。其中一个数据集用于发现，另一个用于验证。选择瘤内和瘤外间质的区域，并比较它们的蛋白信号。在慕尼黑测量的发现数据集中，发现四种蛋白质信号与肿瘤相关基质显著相关。在莱顿测量的独立验证数据集中也检测到其中3个峰，所有这些峰也与肿瘤内基质显著相关。分层聚类显示在慕尼黑MSI数据集中的准确性为100%，在莱顿MSI数据集中的准确性为80.9%。20例乳腺肿瘤的免疫组化结果证实了其中一个质量信号（PA 28）与基质激活的相关性。独立和国际MALDI MSI研究可以识别基质激活的有效生物标志物。
MALDI mass spectrometry imaging (MSI) has rapidly established itself as a powerful biomarker discovery tool. To date, no formal investigation has assessed the center-to-center comparability of MALDI MSI experiments, an essential step for it to develop into a new diagnostic method. To test such capabilities, we have performed a multicenter study focused on biomarkers of stromal activation in breast cancer. MALDI MSI experiments were performed in two centers using independent tissue banks, infrastructure, methods, and practitioners. One of the data sets was used for discovery and the other for validation. Areas of intra- and extratumoral stroma were selected, and their protein signals were compared. Four protein signals were found to be significantly associated with tumor-associated stroma in the discovery data set measured in Munich. Three of these peaks were also detected in the independent validation data set measured in Leiden, all of which were also significantly associated with intratumoral stroma. Hierarchical clustering displayed 100% accuracy in the Munich MSI data set and 80.9% accuracy in the Leiden MSI data set. The association of one of the identified mass signals (PA28) with stromal activation was confirmed with immunohistochemistry performed on 20 breast tumors. Independent and international MALDI MSI investigations could identify validated biomarkers of stromal activation.