HR-MAS NMR Tissue Metabolomic Signatures Cross-validated by Mass Spectrometry Distinguish Bladder Cancer from Benign Disease

Effective diagnosis and surveillance of bladder cancer (BCa) is currently challenged by detection methods that are of poor sensitivity, particularly for low-grade tumors, resulting in unnecessary invasive procedures and economic burden. We performed HR-MAS NMR-based global metabolomic profiling and applied unsupervised principal component analysis (PCA) and hierarchical clustering performed on NMR data set of bladder-derived tissues and identified metabolic signatures that differentiate BCa from benign disease. A partial least-squares discriminant analysis (PLS-DA) model (leave-one-out cross-validation) was used as a diagnostic model to distinguish benign and BCa tissues. Receiver operating characteristic curve generated either from PC1 loadings of PCA or from predicted Y-values resulted in an area under curve of 0.97. Relative quantification of more than 15 tissue metabolites derived from HR-MAS NMR showed significant differences (P < 0.001) between benign and BCa samples. Noticeably, striking metabolic ...