Fig. 3
Urine proteins that discriminate BC stages, based on the aptamer-based proteomic screen. A A volcano plot representation of the results of the aptamer-based screening of 1317 proteins analyzed in 27 urine samples, comparing disease stages (NMIBC = 18, MIBC = 9). Data was log-transformed and analyzed as detailed in the “Methods” section. Eight proteins were found to be elevated (Mann–Whitney p-value < 0.05, fold change > 2) in MIBC when compared to NMIBC. Each dot represents one of the 1317 proteins. The x-axis shows the log2 transform of the fold change. The y-axis displays the − log10 transform of the p-value. B A 2D PCA analysis of all subjects using the top 119 urine proteins (BC vs UC, Mann–Whitney q-value < 0.05). NMIBC are represented by a red circle while MIBC is represented by a blue triangle. Urology control is represented by a green square. The first three principal components are displayed on each axis of the plot. C A Venn diagram comparison of the number of proteins significantly elevated in bladder cancer versus urology control compared to proteins significantly elevated in MIBC compared to NMIBC urine. The data for two different fold change cutoffs are included. D Short Time-series Expression Miner (STEM) analysis was completed for the top 330 proteins (BC vs UC, Mann–Whitney p-value < 0.05). The number in the upper left-hand corner of each box is the number of proteins in each cluster. The number in the lower left-hand corner is the p-value significance of the number of proteins assigned to the cluster versus what was expected based on permutation testing. The protein expression through UC, and progressive BC stages, Ta-Tis, T1, and T2–T4, is plotted. Statistically significant profiles that are similar form a cluster of profiles and are shaded the same color. A total of 50 profiles or clusters (each representing a different pattern) were generated by STEM analysis, of which only the statistically significant clusters that exhibited a progressive increase (clusters 1 and 2) or decrease (clusters 3–6) of urine biomarkers across BC stages are plotted