A set of five proteins that appears to be present in the urine of patients with bladder cancer but not in healthy peers may form the basis for a future test that could detect the disease at an early stage, according to an article in the July 6 issue of the Journal of Proteome Research.

Initially, researchers isolated nearly 200 proteins from the urine of patients with and without bladder cancer. Several showed promise as potential biomarkers, including one that studies conducted elsewhere had already linked to liver and ovarian cancer.

"With any cancer, the earlier you find it the better because it's not as aggressive in its early stages, and of course it's much easier to remove any cancer anywhere in the body if you catch it while it's relatively small," said Steve Goodison, PhD, an associate professor of surgery at the University of Florida College of Medicine-Jacksonville.

The urine tests currently used to detect recurrent bladder cancer miss 60 percent to 75 percent of all malignancies, especially those that are low-grade or early stage.

"They haven't proven to be accurate enough to make the urologists confident to use them instead of doing manual inspection to date (using cystoscopy)," Goodison said. "The trouble is, a lot of tests tend to look at only one biomarker, and one biomarker is never really going to do it, you need to do a panel. You need something like six biomarkers on a dipstick and if four of the six come up then you have an accurate answer. Tests that look at one protein are not going to do it because cancer is so different between individuals."

In the current study, scientists used a technique to search for glycoproteins in urine samples from 10 individuals, five of whom had bladder cancer. Each sample was small, on average about 30 milliliters. In contrast, previous urine protein profiles required large-volume samples.

Of the 186 proteins identified, five were present only in patients with cancer. The findings also substantially add to the urinary proteome database, which until now only contained 146 proteins. Additional studies are planned to screen samples from a larger number of bladder cancer patients with a variety of disease stages and grades.

"Even though our study involved a small number of patients so far, this was really a proof of principle that we can use these new techniques to detect proteins in the urine," Goodison said. "Nobody could do that at this (degree of) sensitivity until now."

"The development of novel non-invasive methods for early detection of bladder cancer is very exciting and represents a major step in (making) routine screening of patients with urological disease feasible in the future," said Nicholas C. Popescu, PhD, chief of the molecular cytogenetics section at the National Cancer Institute's Laboratory of Experimental Carcinogenesis. "In addition, interactions among specific proteins could lead to the development of effective therapy of bladder cancer, a major cause of cancer death worldwide."