title: Diagnostic potential of urinary α1-antitrypsin and apolipoprotein E in the detection of bladder cancer.
abstract: OBJECTIVE
  The ability to reliably diagnose bladder cancer in voided urine samples would be a major advance. Using high throughput technologies, we identified a panel of bladder cancer associated biomarkers with potential clinical usefulness. In this study we tested 4 potential biomarkers for the noninvasive detection of bladder cancer.
  
  
  METHODS
  We examined voided urine specimens from 124 patients, including 63 newly diagnosed with bladder cancer and 61 controls. Concentrations of proteins were assessed by enzyme-linked immunosorbent assay, including α1-antitrypsin, apolipoprotein E, osteopontin and pentraxin 3. Data were compared to the results of urinary cytology and the BTA Trak® enzyme-linked immunosorbent assay based bladder cancer detection assay. We used the AUC of ROC curves to compare the usefulness of each biomarker to detect bladder cancer.
  
  
  RESULTS
  Urinary levels of α1-antitrypsin, apolipoprotein E and bladder tumor antigen were significantly increased in subjects with bladder cancer. α1-Antitrypsin (AUC 0.9087, 95% CI 0.8555-0.9619) and apolipoprotein E (AUC 0.8987, 95% CI 0.8449-0.9525) were the most accurate biomarkers. The combination of α1-antitrypsin and apolipoprotein E (AUC 0.9399) achieved 91% sensitivity, 89% specificity, and a positive and negative predictive value of 89% and 90%, respectively. Multivariate regression analysis highlighted only apolipoprotein E as an independent predictor of bladder cancer (OR 24.9, 95% CI 4.22-146.7, p = 0.0004).
  
  
  CONCLUSIONS
  Alone or in combination, α1-antitrypsin and apolipoprotein E show promise for the noninvasive detection of bladder cancer (OR 24.9, 95% CI 4.22-146.7, p = 0.0004). Larger, prospective studies including more low grade, low stage tumors are needed to confirm these results.
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: Shanti
authors.initials: S
authors.lastname: Ross
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; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000652:urine*; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000652:urine; D016022:Case-Control Studies; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012372:ROC Curve; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012737:Sex Factors; D018709:Statistics, Nonparametric; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D055815:Young Adult; D000515:alpha 1-Antitrypsin / Q000652:urine*
chemical_list: D001057:Apolipoproteins E; D014408:Biomarkers, Tumor; D000515:alpha 1-Antitrypsin; D003404:Creatinine