Detection of Bladder Cancer Using Proteomic Profiling of Urine Sediments

Abstract

We used protein expression profiles to develop a classification rule for the detection and prognostic assessment of bladder cancer in voided urine samples. Using the Ciphergen PBS II ProteinChip Reader, we analyzed the protein profiles of 18 pairs of samples of bladder tumor and adjacent urothelium tissue, a training set of 85 voided urine samples (32 controls and 53 bladder cancer), and a blinded testing set of 68 voided urine samples (33 controls and 35 bladder cancer). Using t-tests, we identified 473 peaks showing significant differential expression across different categories of paired bladder tumor and adjacent urothelial samples compared to normal urothelium. Then the intensities of those 473 peaks were examined in a training set of voided urine samples. Using this approach, we identified 41 protein peaks that were differentially expressed in both sets of samples. The expression pattern of the 41 protein peaks was used to classify the voided urine samples as malignant or benign. This approach yielded a sensitivity and specificity of 59% and 90%, respectively, on the training set and 80% and 100%, respectively, on the testing set. The proteomic classification rule performed with similar accuracy in low- and high-grade bladder carcinomas. In addition, we used hierarchical clustering with all 473 protein peaks on 65 benign voided urine samples, 88 samples from patients with clinically evident bladder cancer, and 127 samples from patients with a history of bladder cancer to classify the samples into Cluster A or B. The tumors in Cluster B were characterized by clinically aggressive behavior with significantly shorter metastasis-free and disease-specific survival.

Detection of Bladder Cancer in Urine Sediments by a Novel Multicolor Fluorescence In Situ Hybridization (Quartet) Test

“…Proteomic profiling has evolved from initial surface-enhanced laser desorption/ionization-based technologies to high-resolution mass spectrophotometry, and reports increasing specificities and sensitivities over the last decade from initially 60% to recently in upper 80% range [27][28][29]. Our own proteomic biomarker studies yielded sensitivity and specificity of 80% and 100%, respectively [30]. The most recent reports utilizing methylation markers and mutational analysis combining multiplex polymerase chain reaction and next-generation sequencing report high specificity and sensitivity of >90% [31,32].…”

Evaluation of Protein Profiling in a Cohort of Egyptian Population with Renal Cell Carcinoma and Benign Kidney Neoplasms

“…It has been studied in ovarian, prostate and bladder (Bauc et al, 2004). Majewski et al, (2012) used the urinary peptide profiling for detection of bladder cancer but he too did not identify the true nature of such peptide peaks.…”

Clinical proteomic biomarkers: relevant issues on study design & technical considerations in biomarker development

“…Based on the literature published, it appears that numerous proteomic biomarkers do exist that will likely result in a substantial improvement of the current clinical situation [ 193 , 194 , 198 ].…”