Novel Proteins as Urinary Biomarkers of Renal Cell Carcinoma

Jeremiah Morrissey Ph.D. and
Evan Kharasch M.D., Ph.D.

Project Overview:
Renal (kidney) cancer is a silent killer. By the time renal cancer causes symptoms which prompt patients to visit their physician, the tumor has usually advanced beyond a curative stage. In the U.S. in 2008, more than 52, 000 new cases of kidney cancer were diagnosed and almost 13,000 patients died from this disease.

There are known risk factors for kidney cancer such as smoking, obesity and hypertension. Unfortunately, there is no test that can be effectively and easily used to screen populations at high risk for developing kidney cancer. This is tragic, because when diagnosed early, surgery often cures the disease and prolongs life first by tumor removal and second by preserving viable kidney function. Previous studies by many groups have characterized gene and protein expression in tumor tissue once it was removed, but this has not translated into any clinically relevant tests to prospectively diagnose kidney cancer.

We propose to develop simple, noninvasive, effective urine tests that can screen large populations for the early diagnosis and treatment of kidney cancer. The goal is to identify novel biomarkers – molecules in urine that are either atypically present or absent that will signal the presence of otherwise undetectable cancers, and allow their early removal. Based on preliminary data, we have found two novel proteins in the urine of patients with kidney cancer that are greatly decreased in their urine after surgery to remove the tumor. These biomarkers will be characterized to determine their sensitivity and specificity to diagnose kidney cancer and to post-surgically follow-up on patients to determine if they remain free from recurrent disease.

The accuracy of the markers to diagnose kidney cancer will be evaluated by comparing the marker levels in age- and sex-matched normal individuals. There is no additional risk to the patients from this study since it involves the collection of urine at the time of surgery and one or two urine samples at the normal post-surgical follow-up visits. In the future, we will develop more inexpensive, high throughput, real-time assays for the biomarkers that can give same-day results. Overall, this investigation has the potential to improve the health of everyone in general and those in at-risk populations by developing a method to detect kidney cancer at a stage early enough to allow a significant chance for cure and preserve existing kidney function, all of which will lead to a longer life.

Final Report Abstract
Based on microarray studies showing that several genes were highly expressed in cancerous compared to normal kidney cells, we hypothesized that novel proteins would be found in high concentrations in the urine of patients with kidney cancer. In an IRB-approved clinical investigation, we found (by Western blotting) markedly increased urine concentrations of aquaporin-1 (AQP-1) and adipophilin (ADRP) in patients with clear cell and papillary carcinomas which together account for over 80 percent of kidney cancers. A month or more after tumor removal the concentration of these two novel proteins decreased to barely or undetectable levels in the patients’ urine. These proteins appear sensitive and specific and, if validated and matured into a clinically useful assay, they would be the first ever non-invasive biomarkers for detecting renal cancer and its recurrence. The specific aim of the proposal was to: Identify candidate novel biomarker proteins in the urine of patients with renal cancer. Read the full Final Report.