Metabolic Reprogramming of Cancer Stem Cells and a Novel Eight-Gene Metabolism-Related Risk Signature in Clear Cell Renal Carcinoma

Abstract

Background:: Clear cell renal carcinoma (ccRCC) is one of the most common urological tumors worldwide and metabolic reprogramming is its distinguishing feature. A systematic study on the role of the metabolism-related genes in ccRCC cancer stem cells (CSCs) is still lacking. Moreover, an effective metabolism-related prediction signature is urgently needed to assess the prognosis of ccRCC patients. Methods:: Gene expression profiles of GSE48550 and GSE84546 were analyzed for the role of metabolism-related gene in ccRCC-CSCs. The GSE22541 dataset were used to construct and validate an effective metabolism-related prediction signature to assess the prognosis of ccRCC patients. Results:: For glycolytic metabolism, we found that HKDC1, PFKM and LDHB were significantly upregulated in ccRCC-CSCs in GSE84546. For TCA cycle, ACO1, SDHA and MDH1 were significantly downregulated in ccRCC-CSCs in both GSE48550 and GSE84546. For fatty acid metabolism, CPT1A and ACACB were significantly upregulated in ccRCC-CSCs in GSE84546. It is worth noting that SCD was significantly downregulated in both GSE48550 and GSE84546. For glutamine metabolism, SLC1A5, GLS and GOT1 were significantly upregulated in GSE84546. An eight-gene CSCs metabolism-related risk signature including HKDC1, PFKM, LDHB, IDH1, OGDH, SDHA, GLS and GLUL were constructed to predict the overall survival (OS) of ccRCC patients. Patients could be separated into two groups, and the patients with lower risk scores had longer survival time. Conclusion:: Our study indicated that metabolic reprogramming, including glycolytic metabolism, TCA cycle, fatty acid metabolism and glutamine metabolism, is more obvious in CD105+ renal cells (GSE84546) than CD133+ renal cells (GSE48550). An eight-gene metabolismrelated risk signature including HKDC1, PFKM, LDHB, IDH1, OGDH, SDHA, GLS and GLUL can effectively predict OS in ccRCC.