Related Experiment Video
Updated: Apr 15, 2026
The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
Published on: January 22, 2013
Analysis and interpretation of transcriptomic data obtained from extended Warburg effect genes in patients with clear
Edward Sanders1, Svenja Diehl2
1Edward Sanders Scientific Consulting, Rue du Clos 33, Peseux, Switzerland.
Background:
Many cancers adopt a metabolism that is characterized by the well-known Warburg effect (aerobic glycolysis). Recently, numerous attempts have been made to treat cancer by targeting one or more gene products involved in this pathway without notable success. This work outlines a transcriptomic approach to identify genes that are highly perturbed in clear cell renal cell carcinoma (CCRCC).
Methods:
We developed a model of the extended Warburg effect and outlined the model using Cytoscape. Following this, gene expression fold changes (FCs) for tumor and adjacent normal tissue from patients with CCRCC (GSE6344) were mapped on to the network. Gene expression values with FCs of greater than two were considered as potential targets for treatment of CCRCC.
Results:
The Cytoscape network includes glycolysis, gluconeogenesis, the pentose phosphate pathway (PPP), the TCA cycle, the serine/glycine pathway, and partial glutaminolysis and fatty acid synthesis pathways. Gene expression FCs for nine of the 10 CCRCC patients in the GSE6344 data set were consistent with a shift to aerobic glycolysis. Genes involved in glycolysis and the synthesis and transport of lactate were over-expressed, as was the gene that codes for the kinase that inhibits the conversion of pyruvate to acetyl-CoA. Interestingly, genes that code for unique proteins involved in gluconeogenesis were strongly under-expressed as was also the case for the serine/glycine pathway. These latter two results suggest that the role attributed to the M2 isoform of pyruvate kinase (PKM2), frequently the principal isoform of PK present in cancer: i.e. causing a buildup of glucose metabolites that are shunted into branch pathways for synthesis of key biomolecules, may not be operative in CCRCC. The fact that there was no increase in the expression FC of any gene in the PPP is consistent with this hypothesis. Literature protein data generally support the transcriptomic findings.
Conclusions:
A number of key genes have been identified that could serve as valid targets for anti-cancer pharmaceutical agents. Genes that are highly over-expressed include ENO2, HK2, PFKP, SLC2A3, PDK1, and SLC16A1. Genes that are highly under-expressed include ALDOB, PKLR, PFKFB2, G6PC, PCK1, FBP1, PC, and SUCLG1.
Insights
This study identifies key genes perturbed in clear cell renal cell carcinoma (CCRCC) metabolism, revealing potential therapeutic targets by analyzing the extended Warburg effect. Over-expressed genes like ENO2 and HK2, and under-expressed genes like ALDOB and PCK1, offer new avenues for cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
- Genomics
Background:
- Many cancers exhibit altered metabolism, notably the Warburg effect (aerobic glycolysis).
- Previous attempts to target Warburg effect genes for cancer treatment have yielded limited success.
- This study focuses on clear cell renal cell carcinoma (CCRCC) and its unique metabolic profile.
Purpose of the Study:
- To identify genes significantly perturbed in CCRCC using a transcriptomic approach.
- To explore potential therapeutic targets by analyzing the extended Warburg effect in CCRCC.
- To investigate the role of specific metabolic pathways in CCRCC development.
Main Methods:
- Developed a computational model of the extended Warburg effect using Cytoscape.
- Mapped gene expression fold changes (FCs) from CCRCC patient tumor and normal tissues onto the network.
- Identified potential therapeutic targets based on gene expression FCs greater than two.
Main Results:
- The network integrated glycolysis, gluconeogenesis, pentose phosphate pathway (PPP), TCA cycle, serine/glycine pathway, glutaminolysis, and fatty acid synthesis.
- Transcriptomic data from 9 out of 10 CCRCC patients showed a shift towards aerobic glycolysis.
- Over-expressed genes involved in glycolysis, lactate synthesis/transport, and pyruvate kinase inhibition were observed; gluconeogenesis and serine/glycine pathway genes were under-expressed.
Conclusions:
- Identified several key genes as potential targets for anti-cancer drug development in CCRCC.
- Highly over-expressed genes include ENO2, HK2, PFKP, SLC2A3, PDK1, and SLC16A1.
- Highly under-expressed genes include ALDOB, PKLR, PFKFB2, G6PC, PCK1, FBP1, PC, and SUCLG1.
