title: Vascular endothelial growth factor, carbonic anhydrase 9, and angiogenin as urinary biomarkers for bladder cancer detection.
abstract: OBJECTIVE
  To investigate whether elevated urinary levels of vascular endothelial growth factor (VEGF), carbonic anhydrase 9 (CA9), and angiogenin are associated with bladder cancer (BCa).
  
  
  METHODS
  This was a case-control study in which voided urine samples from 127 patients (63 control subjects and 64 patients with BCa) were analyzed. The urinary concentrations of VEGF, CA9, angiogenin, and bladder tumor antigen (BTA) were assessed using enzyme-linked immunosorbent assays. We used the area under the curve of receiver operating characteristic curves to determine the ability of VEGF, CA9, and angiogenin to detect BCa in voided urine samples. Data were also compared with the findings from a commercial enzyme-linked immunosorbent assay-based BCa detection assay (BTA-Trak). The sensitivity, specificity, and positive and negative predictive values were calculated.
  
  
  RESULTS
  The urinary concentrations of VEGF, CA9, angiogenin, and BTA were significantly elevated in those with BCa. VEGF was the most accurate urinary biomarker (area under the curve 0.886, 95% confidence interval 0.8301-0.9418). Furthermore, multivariate regression analysis highlighted VEGF (odds ratio 5.90, 95% confidence interval 2.60-13.40, P < .0001) as an independent variable. The sensitivity and specificity for VEGF (83% sensitivity and 87% specificity) outperformed those for BTA (80% sensitivity and 84% specificity).
  
  
  CONCLUSIONS
  VEGF could be a valuable addition to voided urine sample analysis for the detection of BCa. Larger, prospective studies are needed to determine the clinical utility of urinary VEGF and angiogenin as biomarkers in the noninvasive evaluation of patients with BCa.
authors.affiliation: Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, Florida 32806, USA.
authors.forename: Virginia
authors.initials: V
authors.lastname: Urquidi
authors.forename: Steve
authors.initials: S
authors.lastname: Goodison
authors.forename: Jeongsoon
authors.initials: J
authors.lastname: Kim
authors.forename: Myron
authors.initials: M
authors.lastname: Chang
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Dai
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000652:urine*; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000652:urine*; D002277:Carcinoma / Q000175:diagnosis / Q000652:urine*; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D012372:ROC Curve; D012259:Ribonuclease, Pancreatic / Q000652:urine*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000652:urine*; D042461:Vascular Endothelial Growth Factor A / Q000652:urine*; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D042461:Vascular Endothelial Growth Factor A; C112999:bladder tumor-associated antigen; C046366:angiogenin; D012259:Ribonuclease, Pancreatic; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases