Bladder Cancer-associated Protein, a Potential Prognostic Biomarker in Human Bladder Cancer

Abstract

It is becoming increasingly clear that no single marker will have the sensitivity and specificity necessary to be used on its own for diagnosis/prognosis of tumors. Interpatient and intratumor heterogeneity provides overwhelming odds against the existence of such an ideal marker. With this in mind, our laboratory has been applying a long term systematic approach to identify multiple biomarkers that can be used for clinical purposes. As a result of these studies, we have identified and reported several candidate biomarker proteins that are deregulated in bladder cancer. Following the conceptual biomarker development phases proposed by the Early Detection Research Network, we have taken some of the most promising candidate proteins into postdiscovery validation studies, and here we report on the characterization of one such biomarker, the bladder cancer-associated protein (BLCAP), formerly termed Bc10. To characterize BLCAP protein expression and cellular localization patterns in benign bladder urothelium and urothelial carcinomas (UCs), we used two independent sets of samples from different patient cohorts: a reference set consisting of 120 bladder specimens (formalin-fixed as well as frozen biopsies) and a validation set consisting of 2,108 retrospectively collected UCs with long term clinical followup. We could categorize the UCs examined into four groups based on levels of expression and subcellular localization of BLCAP protein and showed that loss of BLCAP expression is associated with tumor progression. The results indicated that increased expression of this protein confers an adverse patient outcome, suggesting that categorization of staining patterns for this protein may have prognostic value. Finally, we applied a combinatorial two-marker discriminator using BLCAP and adipocyte-type fatty acid-binding protein, another UC biomarker previously reported by us, and found that the combination of the two markers correlated more closely with grade and/or stage of disease than the individual markers. The implications of these results in biomarker discovery are discussed.Molecular & Cellular Proteomics 9:161-177, 2010.

Loss of Imprinting as an Epigenetic Marker in Bladder Cancer

“…In support of its role as a tumor suppressor, Fan et al [140] showed that overexpression of BLCAP resulted in growth inhibition and induced apoptosis of human Ewing's sarcoma cells in vitro. In a recent study of 120 patients and validated with 2,108 samples, the authors confirmed that the loss of BLCAP expression is associated with tumor progression, high levels of nuclear protein expression and a poor prognosis, suggesting that BLCAP expression may be a prognostic biomarker [135].…”

“…This gene, also known as BC10 protein (bladder cancer-10 kDa protein), is located at 20q11.23 and encodes a small protein with unknown cellular functions. Although it has no homology to any known protein [135], it includes putative cytoplasmic domains at the N-and C-terminal ends, a SPXX motif and a proline-rich area resembling the PXXP domain, which suggests that it may play a role in cell signaling [136]. Transcriptional down-regulation of this gene has been observed in different tumor types [137-138-139] including invasive bladder cancer [136].…”

Bladder cancer: translating molecular genetic insights into clinical practice

“…In recent years, 5 major proteomic technology platforms have been used: 2-dimensional gel electrophoresis, surface-enhanced laser desorption/ionization, liquid chromatography-mass spectrometry, capillary electrophoresis coupled to mass spectroscopy, and protein arrays [94]. Proteomic studies reportedly have utility in TCC diagnosis [95][96][97], surveillance for recurrence [98,99], prediction of invasive behavior [100,101], and prediction of outcome [100,102].…”

Mucoadhesive polyacrylamide nanogel as a potential hydrophobic drug carrier for intravesical bladder cancer therapy

“…Bladder cancer, ranked among the most common types of cancers worldwide (Chiong et al, 2008;Moreira et al, 2010), has been deemed as one of the most costly to treat because of its long-term propensity of recurrence (Botteman et al, 2003). Among bladder cancers, 70-80% are superficial or non-muscle invasive cancers (NMIBC) (GuhaSarkar and Banerjee, 2010;Ploeg et al, 2009).…”