Maastricht MultiModal Molecular Imaging Institute (M4i), University of Maastricht, Maastricht, The Netherlands.
Department of Surgery, Maastricht University Medical Center+, Maastricht, The Netherlands.
Lab Invest. 2021 Mar;101(3):381-395. doi: 10.1038/s41374-020-00526-w. Epub 2021 Jan 22.
Real-time tissue classifiers based on molecular patterns are emerging tools for fast tumor diagnosis. Here, we used rapid evaporative ionization mass spectrometry (REIMS) and multivariate statistical analysis (principal component analysis-linear discriminant analysis) to classify tissues with subsequent comparison to gold standard histopathology. We explored whether REIMS lipid patterns can identify human liver tumors and improve the rapid characterization of their underlying metabolic features. REIMS-based classification of liver parenchyma (LP), hepatocellular carcinoma (HCC), and metastatic adenocarcinoma (MAC) reached an accuracy of 98.3%. Lipid patterns of LP were more similar to those of HCC than to those of MAC and allowed clear distinction between primary and metastatic liver tumors. HCC lipid patterns were more heterogeneous than those of MAC, which is consistent with the variation seen in the histopathological phenotype. A common ceramide pattern discriminated necrotic from viable tumor in MAC with 92.9% accuracy and in other human tumors. Targeted analysis of ceramide and related sphingolipid mass features in necrotic tissues may provide a new classification of tumor cell death based on metabolic shifts. Real-time lipid patterns may have a role in future clinical decision-making in cancer precision medicine.
基于分子模式的实时组织分类器是用于快速肿瘤诊断的新兴工具。在这里,我们使用快速蒸发电离质谱(REIMS)和多元统计分析(主成分分析-线性判别分析)对组织进行分类,并与金标准组织病理学进行比较。我们探讨了 REIMS 脂质图谱是否可以识别人类肝肿瘤并改善其潜在代谢特征的快速特征描述。基于 REIMS 的肝实质(LP)、肝细胞癌(HCC)和转移性腺癌(MAC)的分类准确率达到 98.3%。LP 的脂质图谱与 HCC 的更相似,而与 MAC 的则不同,因此可以清楚地区分原发性和转移性肝肿瘤。HCC 的脂质图谱比 MAC 的更具异质性,这与组织病理学表型中观察到的变化一致。一种常见的神经酰胺图谱以 92.9%的准确率区分了 MAC 中的坏死与存活肿瘤,以及其他人类肿瘤中的坏死与存活肿瘤。对坏死组织中神经酰胺和相关鞘脂质量特征的靶向分析可能会基于代谢变化为肿瘤细胞死亡提供新的分类。实时脂质图谱可能在癌症精准医学的未来临床决策中发挥作用。