Table 1.
Tumor stage, sample size and age range of data selected from GSE 31684 dataset.
Figure 1.
Flow diagram detailing the methods used to identify genes associated with TCC progression and muscle-invasive behavior from expression microarray data.
Table 2.
KEGG pathway enrichment of genes differentially expressed in T1–T4 staged bladder tumors versus Ta-stage tumors.
Figure 2.
Altered expression in a network of Ras/MAPK associated signaling pathway genes in TCC progression.
The stimulatory and inhibitory interactions of gene products differentially expressed in T1–T4 versus Ta tumors were mapped based on KEGG pathway maps. Node color denotes relative expression: Yellow = Increased expression in muscle-invasive tumors; Blue = Decreased expression in muscle-invasive tumors. Green and red arrows represent stimulatory and inhibitory interactions, respectively. The names of genes with supported associations with muscle-invasive tumors are highlighted in bold italics.
Figure 3.
Expression heatmap of candidate muscle-invasive genes.
Yellow and blue indicate increased and decreased expression in candidate muscle-invasive genes, respectively, relative to the average expression in Ta tumors.
Table 3.
KEGG pathway enrichment of genes differentially expressed in T2 versus Ta and T1 stage bladder tumors.
Figure 4.
Bibliomic associations network in selected gene expression of muscle-invasive versus superficial tumors.
Node color represents change in expression. Edges represent functional associations identified in the literature by text-mining programs PubGene and Chilibot. Selected genes separate into two functional groups of extracellular matrix and signal transduction genes. Black arrows represent generalized groups of outside genes with functional relationships to selected genes in the literature.
Table 4.
Average normalized median expression of selected genes differentially expressed in non-invasive and muscle-invasive TCC in at least 3 datasets within the Oncomine Collection.
Table 5.
Literature-based associations of selected genes and characteristics associated with advanced or metastatic cancers, identified using Chilibot [11].
Figure 5.
Elevated expression of COL3A1 and COL5A1 in muscle-invasive bladder tumors and metatstatic T24 cells.
A. Immunohistochemistry of bladder tumors. DAB (brown) staining represents COL3A1 protein expression, while Warp Red staining represents COL5A1. Results are representative of five independent sample tissues per grade. B. Immunoblot analysis in immortalized non-cancer HUC cells and T24 bladder cancer cells. Expression of COL3A1 and COL5A1 was standardized to that of β-actin, and normalized to expression in HUC cells. These results are representative of 2 independent experiments.
Figure 6.
Model of muscle-invasive bladder cancer based on expression data and published observations.
Arrows represent positive interactions. Black “X”s on arrows represent antagonistic interactions. Red “X”s represent disrupted or decreased activity.