Low- and High-Grade Bladder Cancer Determination via Human Serum-Based Metabolomics Approach.
ABSTRACT 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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ABSTRACT: Early diagnosis and life-long surveillance are clinically important to improve the long-term survival of bladder cancer patients. Currently, a noninvasive biomarker that is as sensitive and specific as cystoscopy in detecting bladder tumors is lacking. Metabonomics is a complementary approach for identifying perturbed metabolic pathways in bladder cancer. Significant progress has been made using modern metabonomic techniques to characterize and distinguish bladder cancer patients from control subjects, identify marker metabolites and shed insights on the disease biology and potential therapeutic targets. With its rapid development, metabonomics has the potential to impact the clinical management of bladder cancer patients in the future by revolutionizing the diagnosis and life-long surveillance strategies and stratifying patients for diagnostic, surgical and therapeutic clinical trials. In this review, introduction to metabonomics, typical metabonomic workflow and critical evaluation of metabonomic investigations in identifying biomarkers for the diagnosis of bladder cancer are presented.Journal of Proteome Research 11/2014; · 5.06 Impact Factor