Detection of bladder cancer using a novel nuclear matrix protein, BLCA-4

We have identified previously six nuclear matrix proteins (NMPs) that are b ladder cancer specific. In this study, we analyzed the expression of one of these proteins, BLCA- 1, in bladder tumors and normal bladder tissue. We a lso examined the appearance of BLCA-4 in the urine as a biomarker for bladd er cancer. BLCA-4 was isolated from nuclear matrix preparations of bladder tumors, and its peptide sequence was determined. The antibodies generated a gainst the resulting BLCA-4 peptides were then used to detect its presence in immunoblots and in urine samples by immunoassay. We analyzed tissue samp les of bladder tumor and normal donor bladders and urine obtained from 51 n ormal individuals and 54 patients with pathologically confirmed bladder can cer. The BLCA-4 peptide sequences do not resemble any known human protein s equences. On immunoblot analysis, BLCA-4 expression was detectable in tumor and normal tissues from patients with bladder cancer but not in any of the normal bladder tissue obtained from organ donors. Using a prospectively de termined cutoff level of 13 A (absorbance) units/pg protein, all 51 normal individuals tested were negative for BLCA-4 expression, whereas 53 of 55 sa mples from patients with bladder cancer were positive. These results sugges t that BLCA-4 is present throughout the bladder in both the tumor and morph ologically normal areas in bladder cancer patients. BLCA-4 is a very sensit ive (96.4%) and specific (100%) marker for bladder cancer. BLCA-4 is a blad der cancer-specific marker that can be detected using a urine-based assay a nd can be used in the diagnosis of bladder cancer.