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Round robin study of formalin-fixed paraffin-embedded tissues in mass spectrometry imaging
Analytical and Bioanalytical Chemistry ( IF 4.3 ) Pub Date : 2018-07-03 , DOI: 10.1007/s00216-018-1216-2
Achim Buck , Bram Heijs , Birte Beine , Jan Schepers , Alberto Cassese , Ron M. A. Heeren , Liam A. McDonnell , Corinna Henkel , Axel Walch , Benjamin Balluff

Mass spectrometry imaging (MSI) has provided many results with translational character, which still have to be proven robust in large patient cohorts and across different centers. Although formalin-fixed paraffin-embedded (FFPE) specimens are most common in clinical practice, no MSI multicenter study has been reported for FFPE samples. Here, we report the results of the first round robin MSI study on FFPE tissues with the goal to investigate the consequences of inter- and intracenter technical variation on masking biological effects. A total of four centers were involved with similar MSI instrumentation and sample preparation equipment. A FFPE multi-organ tissue microarray containing eight different types of tissue was analyzed on a peptide and metabolite level, which enabled investigating different molecular and biological differences. Statistical analyses revealed that peptide intercenter variation was significantly lower and metabolite intercenter variation was significantly higher than the respective intracenter variations. When looking at relative univariate effects of mass signals with statistical discriminatory power, the metabolite data was more reproducible across centers compared to the peptide data. With respect to absolute effects (cross-center common intensity scale), multivariate classifiers were able to reach on average > 90% accuracy for peptides and > 80% for metabolites if trained with sufficient amount of cross-center data. Overall, our study showed that MSI data from FFPE samples could be reproduced to a high degree across centers. While metabolite data exhibited more reproducibility with respect to relative effects, peptide data-based classifiers were more directly transferable between centers and therefore more robust than expected.

中文翻译:

质谱成像中福尔马林固定石蜡包埋组织的循环法研究

质谱成像(MSI)提供了许多具有平移特征的结果,但仍必须在大型患者队列和不同中心进行验证。尽管福尔马林固定石蜡包埋(FFPE)标本在临床实践中最常见,但尚未有关于FFPE标本的MSI多中心研究的报道。在这里,我们报告了对FFPE组织进行的第一轮MSI研究的结果,目的是调查中心间和中心内技术变异对掩盖生物学效应的影响。共有四个中心参与了类似的MSI仪器和样品制备设备。在肽和代谢物水平上分析了包含八种不同类型组织的FFPE多器官组织微阵列,从而能够研究不同的分子和生物学差异。统计分析表明,肽的中心间变异明显低于相应的中心内变异,代谢产物中心间变异显着高于各自的中心内变异。当以统计学上的区分力查看质量信号的相对单变量效应时,与肽数据相比,跨中心的代谢物数据更可重现。关于绝对效应(跨中心共同强度标度),如果使用足够数量的跨中心数据进行训练,则多变量分类器的肽段准确度平均> 90%,代谢产物的平均准确度> 80%。总体而言,我们的研究表明,FFPE样品的MSI数据可以在各个中心之间得到高度复制。尽管代谢物数据在相对影响方面显示出更高的可重复性,
更新日期:2018-07-03
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