Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine

Development of noninvasive methods for the diagnosis of transitional cell c arcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology (surface enhanced laser desorption/ionization time of flight mass spectrom etry) has recently been developed to facilitate protein profiling of biolog ical mixtures. This report describes an exploratory study of this technolog y as a TCC diagnostic tool. Ninety-four urine samples from patients with TC C, patients with other urogenital diseases, and healthy donors were analyze d. Multiple protein changes were reproducibly detected in the TCC group, in cluding five potential novel TCC biomarkers and seven protein clusters (mas s range, 3.3 to 133 kd). One of the TCC biomarkers (3.4 kd) was also detect ed in bladder cancer cells procured from bladder barbotage and was identifi ed as defensin. The TCC detection rates provided by the individual markers ranged from 43 to 70% and specificities from 70 to 86%, Combination of the protein biomarkers and clusters, increased significantly the sensitivity fo r detecting TCC to 87% with a specificity of 66%, Interestingly, this combi natorial approach provided sensitivity of 78% for detecting low-grade TCC c ompared to only 33% of voided urine or bladder-washing cytology, Collective ly these results support the potential of this proteomic approach for the d evelopment of a highly sensitive urinary TCC diagnostic test.