Serum Proteomic Profiling in Patients with Bladder Cancer

Background: Despite continuing research for accurate bladder cancer biomarkers, the analytes suffer from lack of sensitivity and specificity. Objective: To search for discriminating protein patterns in serum, we used magnetic bead-based separation followed by matrix-assisted laser desorption ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) to identify patients with bladder cancer. Design, setting and participants: In total, serum samples from 105 patients with bladder cancer, 98 healthy controls, and 45 prostate cancer patients were included in this study. Measurements: Serum samples were fractionated by means of surface-activated magnetic beads and were subsequently analyzed with MALDI-TOF MS. Multidimensional data analysis was done to generate algorithms capable of distinguishing between cancer patients and healthy individuals. The algorithms were trained using a training set of 41 bladder cancer patients and 39 healthy controls and were validated with an independent test set of 64 bladder cancer patients and 59 healthy controls. Additionally, 45 prostate cancer samples were used as a third test set. Results and limitations: In the training set, patients with bladder cancer could be identified with an overall sensitivity of 94.1% and specificity of 89.2%. Similar results could be achieved for the test set, showing 96.4% sensitivity and 86.5% specificity. Even the presence of low-stage tumors could be predicted with 96% sensitivity and could be distinguished from higher stage or grade tumors with a sensitivity of 77.3%. Distinction between other tumor stages, however, resulted in lower sensitivity values. Conclusions: These findings demonstrate that screening for serum protein patterns using MALDI-TOF MS shows high sensitivity and specificity in identifying patients with bladder cancer, regardless of tumor stage. Due to high-throughput capability, the identified differential protein panel may improve the detection of bladder cancer. (C) 2009 European Association of Urology. Published by Elsevier B. V. All rights reserved.