Low- and high-grade bladder cancer determination via human serum-based metabolomics approach.
To address the shortcomings of urine cytology and cystoscopy for probing and grading urinary bladder cancer (BC), we applied (1)H 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). (1)H 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. (1)H 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.
Department of Urology, King George's Medical University , Lucknow 226003, India.
Navneeta
N
Bansal
Ashish
A
Gupta
Nilay
N
Mitash
Prashant Singh
PS
Shakya
Anil
A
Mandhani
Abbas Ali
AA
Mahdi
Satya Narain
SN
Sankhwar
Sudhir Kumar
SK
Mandal
D000328:Adult; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D003558:Cystoscopy; D016002:Discriminant Analysis; D004311:Double-Blind Method; D006801:Humans; D016018:Least-Squares Analysis; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D060787:Neoplasm Grading; D012372:ROC Curve; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000175:diagnosis
D014408:Biomarkers, Tumor