Prediction of Muscle-invasive Bladder Cancer Using Urinary Proteomics

Abstract

Purpose: Minimally invasive methods of predicting the risk of muscle-invasive urothelial bladder carcinoma may expedite appropriate therapy and reduce morbidity and cost. Experimental Design: Here, capillary electrophoresis coupled mass spectrometry was used to identify urinary polypeptide bladder cancer biomarkers in 127 patients. These markers were used to construct a panel discriminating muscle-invasive from noninvasive disease, which was refined in 297 additional samples from healthy volunteers, patients with malignant and nonmalignant genitourinary conditions. Sequencing of panel polypeptides was then done. Finally, the ability of the panel to predict muscle-invasive disease was evaluated prospectively in 130 bladder carcinoma patients. Four sequenced polypeptides formed a panel predictive of muscle-invasive disease. Conclusions: Use of urinary peptides seems promising in estimating the probability a patient harbors muscle-invasive urothelial bladder cancer. These peptides may also shed novel insights into the biology of bladder tumor progression not obtainable by other methods. Clinical trials seem warranted to evaluate the effect of this approach on practice.

A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy

“…In terms of diagnostic accuracy, CE-MS also favourably compares to urinary Gb 3 , for which an AUC of 0.876 has been reported [33] (vs. 0.970 for CE-MS in our study), although lyso-Gb 3 seems to perform better than total Gb 3 [34]. In addition, because similarly accurate CE-MS based diagnostic models have been developed for a variety of other renal and cardiovascular diseases [13], [35], [36], [37], [38], [39], CE-MS may give hints to an alternative diagnosis in Fabry negative patients, i.e. this approach may offer an efficient diagnostic method, which can detect a variety of diseases using a single diagnostic test.…”

“…We were able to identify nearly one third of differentially excreted peptides. Similar to other diseases that have been studied using CE-MS [35], [36], [38], [39], [40], most diagnostic biomarkers identified represent collagen fragments. Indeed, collagen fragments appear to be the major constituents of urinary peptides identified to date [39].…”

“…Control urine samples were taken from healthy volunteers and patients with a variety of other renal, metabolic and cardiovascular diseases. These samples have been previously collected as part of several clinical studies (refs [13], [35], [36], [37], [38], [39] and as yet unpublished studies). All samples were collected in the morning from midstream urine, frozen at −20°C without prior centrifugation and without addition of protease inhibitors, as suggested in recently published recommendations [42].…”

Bladder Cancer Determination Via Two Urinary Metabolites: A Biomarker Pattern Approach

“…All these urinary markers present challenges for obtaining both high specificity and high sensitivity at the same time (6). Urinary peptides were also evaluated as diagnostic biomarkers, but the reported panel of peptides showed low specificity (8). Although proteins or peptides seem to be promising biomarkers, proteomics or peptidomics approaches are time-consuming, labor-intensive, and costly.…”

A Four-Gene Signature Predicts Disease Progression in Muscle Invasive Bladder Cancer

“…Conventional histopathological parameters such as tumor stage or grade are generally viewed as prognostic factors, and numerous biomarkers have been investigated as prognostic indicators of MIBC (4)(5)(6)(7)(8). However, there are no reliable urinary, histological or stage/grading criteria that can predict disease progression or metastasis of MIBC adequately, or inform the choice of a more aggressive approach to therapy, for example, radical cystectomy.…”