Diagnostic Potential of Urinary α1-antitrypsin and Apolipoprotein E in the Detection of Bladder Cancer

J Urol. 2012 Dec;188(6):2377-83. doi: 10.1016/j.juro.2012.07.094. Epub 2012 Oct 22.

Abstract

Purpose: 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.

Materials and 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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / urine*
  • Biomarkers, Tumor / urine*
  • Carcinoma, Transitional Cell / diagnosis*
  • Carcinoma, Transitional Cell / urine
  • Case-Control Studies
  • Cohort Studies
  • Creatinine / urine
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness / pathology
  • Neoplasm Staging
  • Prognosis
  • ROC Curve
  • Risk Assessment
  • Sensitivity and Specificity
  • Sex Factors
  • Statistics, Nonparametric
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine
  • Young Adult
  • alpha 1-Antitrypsin / urine*

Substances

  • Apolipoproteins E
  • Biomarkers, Tumor
  • alpha 1-Antitrypsin
  • Creatinine