Figure 5. Comparative transcriptomic analyses of murine and human tRCC.
(A) Principal component analysis (PCA) representation of normalized gene expression read counts of kidney tumors (KT), retro-orbital tumors (ROT), intracranial brain tumors (BT), and non-tumor kidney (NTK) from Sglt2-Cre; ASPSCR1-TFE3LSL/+ mice (or adult Sglt2-Cre kidney controls) as well as deformed kidneys from Pax8-Cre; ASPSCR1-TFE3LSL/+ fetuses and fetal kidney controls (Pax8-Cre). (B) GSEA for Hallmark or KEGG gene signatures exhibiting top upregulated and downregulated pathways enriched in murine and human tRCC. NES, normalized enrichment score; FDR, false discovery rate. (C) PCA plot representation of normalized gene expression read counts for the UTSW pan-RCC cohort — tRCC (n = 19), clear cell RCC (ccRCC) (n = 193), papillary RCC (pRCC) (n = 55), and chromophobe RCC (chRCC) (n = 43) — and tumor-matched normal kidney (n = 179). (D) Venn diagram of significantly upregulated genes in human and murine tRCC. (E) Venn diagram of significantly downregulated genes in human and murine tRCC. (F) Venn diagram of SFPQ-TFE3 and NONO-TFE3 direct target genes from 2 independent ChIP-Seq studies. (G) Venn diagram of significantly upregulated genes in human/mouse tRCC and their interaction with shared (SFPQ-TFE3 and NONO-TFE3) direct target genes. Hypergeometric tests were carried out to test the overlap between gene expression signatures (D, E, and G). (H and I) Volcano plots of differentially expressed genes in human (H) and murine (I) tRCC. Green, downregulated genes; red, upregulated genes; gray, unchanged genes. Putative direct targets of MiT/TFE fusion protein are marked.