Figure 2
Validation of the LundTax classifier in the TCGA cohort. Cases in the TCGA cohort were grouped according to the LundTax classifier. Eleven gene signatures were then used to identify different tumor related features. (A) Stromal and immune cells signatures. Stromal and immune score bars show the estimated scores for tumor purity based on the ESTIMATE tool12. High score (red) indicate high-level infiltration; low score (blue) indicate low-level infiltration. (B) Transcription factors involved in urothelial cell differentiation13. (C) Cytokeratin and uroplakin genes10. (D) Genomic circuit genes14 that distinguish the GU subtype from the Uro subtype. Circuit ratios were calculated for each sample as RB1 + FGFR3 + CCND1 − E2F3 − CDKN2A using log2 mRNA expression values. High ratio (red) indicate Uro, low ratio (blue) indicate GU. (E) The FGFR3 gene expression signature10. (F) Expression of the KRT5, KRT14, FOXA1, and GATA3 genes, defining the Basal/Squamous-like (Ba/Sq) molecular subtype16. Ba/Sq ratios were calculated for each sample as KRT5 + KRT14 − FOXA1 − GATA3 using log2 mRNA expression values. High ratio (red) indicate a Ba/Sq subtype, low ratio (blue) indicate non-Ba/Sq subtype. (G) Keratinization gene signature13. (H) The cell adhesion genes EPCAM, CDH1, and CDH3. (I) The expression of the receptor tyrosine kinases EGFR, ERBB2 and ERBB3. ERBB ratios were calculated for each sample as EGFR-ERBB2-ERBB3 using log2 mRNA expression values high ratio (red) indicate EGFR expression >ERBB2 and ERBB3 expression, low ratio (blue) indicate the opposite. Gene expression color codes; red, high expression; green, low expression. Vertical lines separate major molecular subtypes; dotted lines separate subgroups of subtypes. Subtype abbreviations as in Fig. 1.
