A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer

PLoS One. 2012;7(10):e47469. doi: 10.1371/journal.pone.0047469. Epub 2012 Oct 19.

Abstract

Accurate urinary assays for bladder cancer (BCa) detection would benefit both patients and healthcare systems. Through genomic and proteomic profiling of urine components, we have previously identified a panel of biomarkers that can outperform current urine-based biomarkers for the non-invasive detection of BCa. Herein, we report the diagnostic utility of various multivariate combinations of these biomarkers. We performed a case-controlled validation study in which voided urines from 127 patients (64 tumor bearing subjects) were analyzed. The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection. Further validation studies are under way to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / urine*
  • Biomarkers, Tumor / urine*
  • Carcinoma / diagnosis
  • Carcinoma / pathology
  • Carcinoma / urine*
  • Case-Control Studies
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-8 / urine*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • ROC Curve
  • Urinary Bladder / metabolism*
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / diagnosis
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*
  • Vascular Endothelial Growth Factor A / urine*

Substances

  • Apolipoproteins E
  • Biomarkers, Tumor
  • Interleukin-8
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A