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Low- and High-Grade Bladder Cancer Determination via Human Serum-Based Metabolomics Approach

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journal contribution
posted on 06.12.2013, 00:00 authored by Navneeta Bansal, Ashish Gupta, Nilay Mitash, Prashant Singh Shakya, Anil Mandhani, Abbas Ali Mahdi, Satya Narain Sankhwar, Sudhir Kumar Mandal
To address the shortcomings of urine cytology and cystoscopy for probing and grading urinary bladder cancer (BC), we applied 1H nuclear magnetic resonance (NMR) spectroscopy as a surrogate method for the identification of BC. This study includes 99 serum samples comprising low-grade (LG; n = 36) and high-grade (HG; n = 31) BC as well as healthy controls (HC; n = 32). 1H NMR-derived serum data were analyzed using orthogonal partial least-squares discriminant analysis (OPLS-DA). OPLS-DA-derived model validity was confirmed using an internal and external cross-validation. Internal validation was performed using the initial samples (n = 99) data set. External validation was performed on a new batch of suspected BC patients (n = 106) through a double-blind study. Receiver operating characteristic (ROC) curve analysis was also performed. OPLS-DA-derived serum metabolomics (six biomarkers, ROC; 0.99) were able to discriminate 95% of BC cases with 96% sensitivity and 94% specificity when compared to HC. Likewise (three biomarkers, ROC; 0.99), 98% of cases of LG were able to differentiate from HG with 97% sensitivity and 99% specificity. External validation reveals comparable results to the internal validation. 1H NMR-based serum metabolic screening appears to be a promising and less invasive approach for probing and grading BC in contrast to the highly invasive and painful cystoscopic approach for BC detection.