Title:Metabolic Reprogramming of Cancer Stem Cells and a Novel Eight-Gene
Metabolism-Related Risk Signature in Clear Cell Renal Carcinoma
Volume: 4
Issue: 1
Author(s): Lu Pang, Yanfeng Hou, Xin Wang, Jialin Du, Haiming Huang, Mingyu Yang, Sisi Wang, Chongwen An, Tao Meng and Haixia Li*
Affiliation:
- Department of Clinical Laboratory, Peking University First Hospital, Beijing, China
Keywords:
Clear cell renal carcinoma, cancer stem cells, metabolic reprogramming, risk signature, overall survival, novel eight-gene metabolism.
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.