Extended Data Figure 4. FGF-21 is increased in renal cell carcinoma due to increased circulating VEGF.

(A) Photos of kidneys from the same mouse, injected with PBS (left) or with Renca cells (right), and a lung from a Renca tumor-bearing mouse, stained with India ink. Metastases appear white. (B) Tumor Vegfa and Fgf21 mRNA expression in human renal cell carcinoma (n=877 for both proteins). Data from the Human Protein Atlas⁴³. FKPM, fragments per kilobase of transcript per million mapped reads. (C) Tissue FGF-21 protein, measured by ELISA (n=6 liver, 6 kidney, and 5 tumor). (D) Plasma FGF-21 concentrations in mice injected with Renca cells into the renal cortex that did not ultimately grow out a palpable tumor (n=5 on day 0, and 6 on all subsequent days). (E) Survival of RCC patients whose tumors were in the upper and lower quartile (n=219 per quartile) for Vegfa expression. (F) Plasma VEGF concentrations in mice injected with Renca cells into the renal cortex that did not ultimately grow out a visualized tumor (n=6). (G) Plasma VEGF concentrations in mice with Renca RCC tumors (n=5 per timepoint until week 3, at which n=4). (H) Plasma NEFA concentrations in mice injected with recombinant VEGF (n=5 per group). In all panels, *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.