Fig. 3

Integrated multi-omics analyses of tumor tissues compared with MNUs. A Differentially expressed genes, proteins and phosphoproteins in tumors and MNUs and their associated biological pathways (top panel). A list of urothelial bladder signature proteins that were differentially expressed in tumors and MNUs (p value from Wilcoxon rank-sum test) (bottom panel). B Two proteins (UPK3BL and UPK3A) were significantly associated with prognosis (overall survival) (p value from log-rank test). C Fold changes of genes and proteins in tumors and MNUs (Spearman's r = 0.26, p = 2.2E−16) (left) and pathways enriched for respective specific changed molecules (right). D Boxplot showing the mRNA–protein correlations for the genes associated with significant and nonsignificant differences in patient survival at the protein or mRNA level (p value from Kruskal–Wallis test). E Pathways enriched for genes with survival differences at protein or mRNA level. F Fold changes of proteins and phosphosites, and their correlations in tumors and MNUs. Red dots: phosphosites are greater than twofold changes in tumors compared to MNUs, and changes of phosphosites abundance are greater than changes of their corresponding protein abundance. G Pathways enriched with cancer-related phosphosites. H KSEA analyses of kinase activities in tumors and MNUs. I Heatmap of activated kinases in tumors and substrates corresponding to associated biological pathways (left). Inferred activity was calculated via KSEA analyses, and purple boxes indicate the existence of an FDA-approved drug. (J and K) Strategy for candidate target genes (J) and heatmap showing the proteins that meet the screening criteria (K). Cancer dependency map-supported (https://depmap.org) panels on the right show log2-transformed relative survival averaged across all available urinary tract cell lines after depletion of the indicated gene (rows) by RNAi or CRISPR. Their presence in serum was annotated from Plasma Proteome Database (PPD), and drug targets were based on the Drug Gene Interaction Database (http://www.dgidb.org/). L Overview of significantly enriched pathways in tumors and MNUs