The survival rates for patients diagnosed with renal cell carcinoma (RCC) -the most common type of kidney cancer- are extremely low. A major reason is that early-stage RCC is usually asymptomatic leading to a high frequency of patients that present already with metastatic disease. No clinically relevant marker is available that would allow the detection of early-stage RCC. Ideally, a screening assay for RCC should be non-invasive, and should be possible to be developed into a cost-effective, high-throughput assay. An RCC-specific urinary marker may fulfill these criteria. Our preliminary results indicate that urine from RCC patients contains increased levels of matrix metalloproteinase (MMP) activity which causes the degradation of normally excreted extracellular matrix (ECM) proteins. In a preliminary analysis, the detection of the absence of urinary ECM proteins has allowed the detection of RCC with a sensitivity of 95% (21/22) and specificity of 95% (21/22). Importantly, all early-stage cases were correctly identified. The over-all goal of this project is to develop a rapid screening assay based on the detection of urinary MMPs or MMP activity, and to test its clinical usefulness for the detection of RCC. First, the excreted MMP(s) will be identified using specific antibodies or by affinitychromatography and sequencing. Second, a micro-titer plate screening assay will be developed based on the degradation of fluorogenic substrates and/or on the immunological detection of MMPs. Third, using larger RCC patient and control populations, the sensitivity and specificity of the developed screening assay(s) will be determined. ? ?
