Figure 5.

Lipid metabolism in human ccRCC by tumor stage. The metabolomics (n = 138) (Panel A), transcriptomics (n = 533) (Panel B), and somatic copy number data (n = 418) (Panel D) of stage I, II, III, and IV ccRCC were analyzed. Statistical significance was assessed by the two-sided Student's t-test and Pearson's correlation. A illustrates the levels (log2 normalized abundance) of two essential fatty acids (linoleic and linolenic acid) and intermediates of lipid biosynthesis (glutamine, palmitic acid) as measured by LC-MS/MS. A statistically significant (p < 0.05) increase in essential fatty acids and lipid biosynthesis intermediates was detected in stage I ccRCC tumors as compared with the normal kidney tissue. As stage increased, the level of linoleic acid decreased (p < 0.05), while no significant changes in the glutamine or palmitic acid levels were observed. B illustrates levels of CD36 and FASN mRNA levels (RNA-Seq by Expectation Maximization [RSEM]) by tumor stage. CD36 mRNA levels decreased with increasing tumor stage, while the FASN transcript levels increased with tumor stage. C shows the association between CD36 and FASN mRNA levels within each individual patient with ccRCC. An inverse association was found between the CD36 and FASN expression levels. D shows the CD36 and FASN mRNA levels in patients with or without a HIF1A somatic copy number reduction. We found higher CD36 mRNA levels in patients with wild-type (WT) HIF1A. Collectively, these results suggest that HIF1α increases dietary lipid uptake in patients with early stage ccRCC, while tumors in patients with advanced ccRCC may rely on lipid biosynthesis.