Pre-operative urinary cathepsin D is associated with survival in patients with renal cell carcinoma

BACKGROUND: No circulating markers are routinely used for renal cancer. The objective of this pilot study was to investigate whether conditioned media ( CM) from renal cancer cell lines contains potential biomarkers that, when measured in clinical fluids, have diagnostic or prognostic utility. METHODS: Comparative 2D PAGE profiling of CM from renal cell carcinoma (RCC) and normal renal cultures identified cathepsin D that was subsequently validated in urine samples from 239 patients and healthy and benign disease subjects. RESULTS: Urinary cathepsin D was found to be significantly associated with overall ( OS) ( hazard ratio, HR, 1.33, 95% CI [1.09-1.63], P = 0.005) and cancer-specific survival (HR 1.36, 95% CI [1.07-1.74], P = 0.013) in RCC patients on univariate analysis. An optimal cut point ( 211 ng ml(-1) mmol Cr-1) around which to stratify patients by OS was determined. Five-year OS equal to/above and below this value was 47.0% (95% CI 35.4%, 62.4%) and 60.9% (48.8%, 76.0%), respectively. On multivariable analysis using pre-operative variables, cathepsin D showed some evidence of independent prognostic value for OS ( likelihood ratio test P-value = 0.056) although requiring further validation in larger patient numbers with sufficient statistical power to determine independent significance. CONCLUSION: These data establish an important proof of principle and show the potential of proteomics-based studies. Cathepsin D may be of value as a pre-operative urinary biomarker for RCC, alone or in combination. British Journal of Cancer ( 2009) 101, 1175-1182. doi:10.1038/sj.bjc.6605250 www.bjcancer.com (C) 2009 Cancer Research UK