Development of a test to identify bladder cancer in the urine of patients using mass spectroscopy and subcellular localization of the detected proteins

摘要

The survival rate for bladder cancer is much better when the disease is detected early, so improvements in methodology for early detection would be beneficial. When urine contains neoplastic urothelial cells, it carries biomarkers of the disease. This study aims to develop a test for the detection of urothelial carcinoma in the urine. The sediments from urines of ten patients with carcinoma and ten randomly selected normal controls were tested for cancer biomarkers using high-resolution mass spectroscopy. 212 unique individual proteins were identified. Most of them occurred only once or twice in the entire cohort of cases. When sorting the detected proteins by their subcellular compartments, we were able to develop a test that differentiates between the two sets. When the combination of nuclear and red blood cell proteins was used as the discriminating function, the level of statistical significance was p=0.003, the sensitivity was 90%, the specificity 67% and the area under the Receiver-Operating Characteristic curve (ROC) was 94%. When the lack of any detectible proteins, which includes nuclear proteins, was included as a criterion indicating benign urine, the specificity increased to 80%. This use of cellular compartment localization of the detected proteins in the discriminating function is less restrictive than requiring the presence of specific proteins, and we were able to develop a screening test with this less stringent criterion. This approach can be applied to other tumors, such as breast, lung and colon cancers, where the need for a simple screening test is even greater.