Characterization of Current and Novel Biomarkers of Bladder Cancer

Bladder cancer is one of the most common cancers in industrialized countries. It is reported that 3.51 billion dollars are spent each year on bladder cancer treatment making it the most expensive cancer to treat on a per patient basis. Approximately 80% of bladder cancer patients have at least one reported recurrence thereby prompting meticulous lifetime screening and surveillance by health care professionals. Early diagnosis of genitourinary malignancies is a challenging process. Currently, FISH is the gold standard for genetic analysis of bladder cancer as researchers found that utilizing fluorescence in situ hybridization (FISH) technology produced sensitivity from 60–75%. This test is used in conjunction with the traditional noninvasive cytology analysis, which has a sensitivity ranging from 30–50% depending on disease state, and cystoscopy. Therefore, for diagnostic purposes, molecular analysis of gene expression in urine sediment could be useful. Since the distinction between healthy and diseased individuals may depend on the definition of a standard discriminative mRNA threshold level a group of markers is needed to provide a convincing screening tool. Our aim was to elucidate apoptosis regulating gene expression in patient bladder cancer urine samples and to determine their usefulness as bladder cancer diagnostic markers. To perform this study we analyzed 50 urine samples by real-time PCR. The markers analyzed included BIRC3, BIRC4, SURVIVIN, BIRC6, BFAR, NAIP, STANNIN, and APIS. APIS, BIRC3, BIRC4, SURVIVIN, and BFAR provided the most promising data with sensitivity and specificity percentages all ranging at or above 70% except for BIRC8. From this study of bladder cancer markers we initiated a functional study to characterize the novel antiapoptotic protein APIS and its role in bladder cancer initiation and progression. We have characterized APIS expression in human bladder cancer tissues using various analyses. Our data indicated that APIS is expressed early in tumorigenesis, which makes it an ideal early diagnostic marker and displays interesting isoform specific shifts in expression throughout bladder tumorigenesis. In conclusion, detection of apoptosis regulating genes is a promising diagnostic approach.