CCL18 in a multiplex urine-based assay for the detection of bladder cancer, "Beyond the Abstract," by Charles J. Rosser, MD

BERKELEY, CA (UroToday.com) - 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 (CCL-18, PAI-1 and CD44), three markers from our recently published article in PLoSONE 2012) were assessed by enzyme-linked immunosorbent assay (ELISA). Other biomarkers from the panel of 14 included, VEGF, CA-9, ANG, IL-8, MMP-9, MMP-10, SDC1, A1AT, OPN, PTX3, and APOE. Diagnostic performance of each biomarker and multivariate models were compared using receiver-operating characteristic curves and the chi-square test. Urinary concentrations of CCL-18 and PAI-1 were significantly elevated in subjects with BCa. From the three biomarkers, CCL18 was the most accurate biomarker (AUC; 0.919; 95% confidence interval [CI], 0.8704-0.9674). Multivariate regression analysis highlighted CCL-18 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. 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. Larger, validation studies using more diverse clinical samples are underway to investigate the clinical utility of this panel of biomarkers for BCa diagnosis and disease monitoring.

 


Written by:

Charles J. Rosser, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Section of Urologic Oncology, MD Anderson Cancer Center Orlando, Orlando, Florida USA and,
Nonagen Bioscience Corp, Orlando, Florida USA 


 

CCL18 in a multiplex urine-based assay for the detection of bladder cancer - Abstract

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