Urine protein biomarker VEGF aids bladder cancer diagnosis
MedWire News: The noninvasive diagnosis of bladder cancer could be aided by protein analysis of vascular endothelial growth factor (VEGF) in voided urine, results of a case-control study show.
The sensitivity and specificity of VEGF for detecting bladder cancer was 83% and 87% respectively - an accuracy "at least as great" as that achieved using the existing bladder tumor antigen (BTA-Trak) assay, note Charles Rosser (MD Anderson Cancer Center, Orlando, Florida, USA) and colleagues.
Cystoscopy is the reference standard for evaluation of individuals in whom bladder cancer is suspected and for surveillance in patients with a history of bladder cancer. The procedure can be uncomfortable, which can lead to problems with compliance. It also has a false-negative rate of 10-40%.
Voided urinary cytology (VUC) has been widely accepted as an adjunct to cystoscopy. Although VUC has a specificity greater than 93%, its sensitivity has been disappointing at 25-40%, especially for low-grade and low-stage tumors.
In an effort to find better biomarkers, Rosser et al previously performed genomic analyses, finding a transcriptomic diagnostic signature with 14 candidates - including VEGF, angiogenin, and CA9 - that achieved a specificity of 100% at 90% sensitivity.
In the present study, the researchers assessed whether commercial antibodies to the protein products of these candidate biomarkers could facilitate the noninvasive detection of bladder cancer in voided urine.
They took samples from 64 patients with bladder cancer and 63 matched controls. The urinary concentrations of VEGF, CA9, angiogenin, and BTA were assessed using enzyme-linked immunosorbent assays (ELISA).
For all biomarkers tested, the median urinary levels were significantly greater in those with bladder cancer than in controls, with VEGF at 335.34 versus 0 pg/mL; CA9 10.36 versus 0 pg/mL; angiogenin 410.98 versus 44.58 pg/mL; and BTA 179.34 versus 12.55 U/mL.
Urinary VEGF was the most accurate biomarker for detecting bladder cancer with an area under the curve of 0.886, sensitivity of 83%, specificity of 87%, positive predictive value of 87%, and negative predictive value of 83%.
Urinary angiogenin was the next most accurate biomarker with a sensitivity of 67%, specificity of 97%, positive predictive value of 96%, and negative predictive value of 74%.
Using multivariate logistic regression analysis, only elevated urinary VEGF was an independent predictor for bladder cancer (odds ratio=5.90), after adjustment for the effects of age and gender.
"We believe our global biomarker discovery and validation schema, along with the analysis of a panel of viable biomarkers, could prove beneficial in screening for bladder cancer, assessing symptomatic patients (ie, voiding symptoms or hematuria) for bladder cancer, and surveillance after tumor resection," Rosser et al comment in Urology.
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By Andrew Czyzewski