Presentation description

Clear cell renal cell carcinoma (ccRCC), the most common subtype of kidney cancer, has been closely linked to obesity, and altered lipid metabolism is known to play a role in ccRCC development. Ceramides are bioactive lipids involved in cell signaling and may serve as key intermediates connecting obesity to metabolic dysfunction including chronic kidney disease, diabetes, and liver dysfunction. We hypothesize that ceramides are obligate intermediates linking lipid excess to the progression of ccRCC. The KidneyCare Study is a prospective cohort of patients with stage I-IV patients with renal masses undergoing nephrectomy. At the time of surgery, normal kidney, tumor, and adjacent perirenal fat were collected from 110 patients. Tissues were flash frozen for downstream transcriptomics, metabolomics, and lipidomics analyses. To our knowledge, this is one of the largest multi-omic ccRCC studies in existence. We analyzed 298 normal and tumor samples, focusing on 786 lipids, and we then performed differential expression analysis. The mean age was 62.1 (15.2) and 45 (40.9%) of patients were obese. A total of 558 lipids were differentially expressed between normal and tumor tissues (t-test padj 1.5 fold-change). Among the differentially expressed sphingolipids, several ceramides were upregulated in ccRCC and hexosylceramide downregulated. These findings suggest that altered sphingolipid shows an increase in pro-apoptotic lipid-signaling and a reduced glycosphingolipid synthesis in ccRCC. In the future we will be incorporating RNA sequencing and metabolomics data to further understand the role of sphingolipid metabolism in ccRCC progression.