B3
Proteomic identification of two urinary proteins with prognostic value in patients with renal cell carcinoma
Naveen Vasudev, Sheryl Sim, David Cairns, Rosiean Ferguson, Anthea Stanley, Peter Selby, Rosamonde Banks
Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, UK
Background
The discovery of circulating biomarkers in renal cell carcinoma (RCC) is a priority area for research. Such markers may aid in determining diagnosis, prognosis, and predicting response to therapy. We have applied proteomics to the study of biological fluids in RCC towards this goal.
Method
The proteome of growth media conditioned by renal cultures in vitro were compared using 2D-polyacrylamide gel electrophoresis (2D-PAGE). Differentially expressed proteins were identified by tandem mass spectrometry. Two candidate makers were subsequently validated by Enzyme Linked Immunosorbent Assay (ELISA) in a large number (n>200) of urine samples from patients with newly diagnosed conventional RCC and healthy controls.
Results
Two proteins were found to be secreted in greater amounts by tumour cells than their normal counterparts. When assayed in urine (149 RCCs; 60 healthy controls; 30 benign urological disease), the first following normalisation by urinary creatinine was found to be significantly associated with overall (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). The second candidate marker, assayed in 179 samples, was found to have value as a predictor of relapse-free survival (HR 1.81 95%CI [1.11-2.97], p=0.018), with independent prognostic ability on multivariate analysis.
Conclusion
These findings are novel, with the potential to directly impact on patient treatment, follow-up and outcome. Marker 1 is the subject of a CR-UK patent application, making its identity available in October. Further validation of Marker 2 is ongoing and these results, together with a combined analysis, will also be presented.
