CCL18 in a Multiplex Urine-Based Assay for the Detection of Bladder Cancer

PLoS One. 2012;7(5):e37797. doi: 10.1371/journal.pone.0037797. Epub 2012 May 21.

Abstract

The early detection of bladder cancer (BCa) is pivotal for successful patient treatment and management. Through genomic and proteomic studies, we have identified a number of bladder cancer-associated biomarkers that have potential clinical utility. In a case-control study, we examined voided urines from 127 subjects: 64 tumor-bearing subjects and 63 controls. The urine concentrations of the following proteins were assessed by enzyme-linked immunosorbent assay (ELISA); C-C motif chemokine 18 (CCL18), Plasminogen Activator Inhibitor 1 (PAI-1) and CD44. Data were compared to a commercial ELISA-based BCa detection assay (BTA-Trak©) and voided urinary cytology. We used analysis of the area under the curve of receiver operating characteristic curves to compare the ability of CCL18, PAI-1, CD44, and BTA to detect BCa in voided urine samples. Urinary concentrations of CCL18, PAI-1, and BTA were significantly elevated in subjects with BCa. CCL18 was the most accurate biomarker (AUC; 0.919; 95% confidence interval [CI], 0.8704-0.9674). Multivariate regression analysis highlighted CCL18 (OR; 18.31; 95% CI, 4.95-67.70, p<0.0001) and BTA (OR; 6.43; 95% CI, 1.86-22.21, p = 0.0033) as independent predictors of BCa in voided urine samples. The combination of CCL18, PAI-1 and CD44 improved the area under the curve to 0.938. Preliminary results indicate that CCL18 was a highly accurate biomarker for BCa detection in this cohort. Monitoring CCL18 in voided urine samples has the potential to improve non-invasive tests for BCa diagnosis. Furthermore using the combination of CCL18, PAI-1 and CD44 may make the model more robust to errors to detect BCa over the individual biomarkers or BTA.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / urine*
  • Case-Control Studies
  • Chemokines, CC / urine*
  • Early Detection of Cancer / methods*
  • Female
  • Humans
  • Hyaluronan Receptors / urine
  • Male
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / urine
  • Sensitivity and Specificity
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / urine

Substances

  • Biomarkers, Tumor
  • CCL18 protein, human
  • Chemokines, CC
  • Hyaluronan Receptors
  • Plasminogen Activator Inhibitor 1