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

Journal of Proteome Research (Impact Factor: 4.25). 11/2013; 12(12). DOI: 10.1021/pr400859w
Source: PubMed


To address the shortcomings of urine cytology and cystoscopy for probing and grading of urinary bladder cancer (BC), we applied 1H-nuclear magnetic resonance (NMR) spectroscopy as a surrogate method for identification of BC. This study includes 99 serum samples; comprising low-grade (LG, n=36) and high-grade (HG, n=31) of BC, and 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 initial samples (n=99) data set. External validation was performed on new batch of suspected BC patients (n=106) through double blind study. Receiver operating characteristic (ROC) curve analysis was also performed. OPLS-DA-derived serum metabolomics (6 biomarkers, ROC; 0.99) were able to discriminate 95% of BC cases with 96% sensitivity and 94% specificity when compared to HC. Likewise (3 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 internal validation. 1H NMR-based serum metabolic screening appears to be a promising and least-invasive approach for probing and grading of BC in contrast to the highly invasive and painful cystoscopic approach of BC detection.

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    • "In other words, the metabolic pathways associated with BC cells are complex. The studies revealed that lactic acid is upregulated in BC sample23242526. This phenomenon may be attributed to the Warburg effect[34], which states that cancer cells exhibit increased dependence on glycolytic pathway for ATP generation and gives rise to enhanced lactic acid production[35]. Such acidic condition in tumor microenvironment promotes tumor invasion and suppresses anticancer immune effectors363738. "
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