Bladder Cancer Associated Glycoprotein Signatures Revealed by Urinary Proteomic Profiling

Abstract

Current methods in the noninvasive detection and surveillance of bladder cancer via urine analysis include voided urine cytology (VUC) and some diagnostic urinary protein biomarkers; however, due to the poor sensitivity of VUC and high false-positive rates of currently available protein assays, detection of bladder cancer via urinalysis remains a challenge. In the study presented here, a rapid, high-sensitivity technique was developed to profile the N-linked glycoprotein component in naturally micturated human urine specimens. Concanavalin A (Con A) affinity chromatography coupled to nanoflow liquid chromatography was utilized to separate the complex peptide mixture prior to a linear ion trap MS analysis. Of 186 proteins identified with high confidence by multiple analyses, 40% were secreted proteins, 18% membrane proteins, and 14% extracellular proteins. In this study, the presence of several proteins appeared to be associated with the presence of bladder cancer, including R-1B-glycoprotein that was detected in all tumor-bearing patient samples but in none of the samples obtained from nontumor-bearing individuals. The combination of Con A affinity chromatography and nano-LC/MS/MS provides an initial investigation of N-glycoproteins in complex biological samples and facilitates the identification of potential biomarkers of bladder cancer in noninvasively obtained human urine.

Proteomic Changes Induced by Effective Chemopreventive Ratios of n-3:n-6 Fatty Acids and Tamoxifen against MNU-Induced Mammary Cancer in the Rat

“…Proteins such as VDBP and A1BG were differentially altered in a manner consistent with chemoprevention (13)(14)(15)(16). VDBP was found to be upregulated, whereas A1BG was downregulated in response to increasing levels of n-3 fatty acids.…”

“…In pancreatic juice and pancreatic tissue of pancreatic cancer patients, A1BG was upregulated in comparison to cancerfree controls (39). A1BG has also been shown to be elevated in the urine of bladder cancer patients compared to controls (16).…”

Intestinal proteome changes during infant necrotizing enterocolitis

“…The role of this protein remains unclear apart from its known role in fattyacid absorption and transport and in local nervous system and regulation of water permeability (32). A protein with increased intestinal expression in NEC, α1 B-glycoprotein, is elevated in pancreatic juice from patients with pancreatic ductal adenocarcinoma and in hepatocellular carcinoma cell lines and liver tumor tissue samples (33,34). Similarly, the marked expression increase in local intestinal and colonic immunoglobulin production might result in elevated circulating levels of the same components.…”

Breast tumor metastasis: analysis via proteomic profiling

“…Further investigation into the functional role of specific proteins identified in these comparative proteomic studies is under way in our laboratory. We are also using MDA-MB-435 and MCF10A metastasis models to develop the coupling of 2D liquid separation methods to protein microarray technology, particularly the glycoprotein and phosphoprotein subproteomes, in order to apply them to cancer models and human tissue samples [66].…”