Abstract
Cancer-dependent metabolic rewiring is often manifested by selective expression of enzymes essential for the transformed cells’ viability. However, the metabolic variations between normal and transformed cells are not fully characterized, and therefore, a systematic analysis will result in the identification of unknown cellular mechanisms crucial for tumorigenesis. Here, we applied differential gene expression transcriptome analysis to examine the changes in metabolic gene profiles between a wide range of normal tissues and cancer samples. We found that, in contrast to normal tissues which exhibit a tissue-specific expression profile, cancer samples are more homogenous despite their diverse origins. This similarity is due to a “proliferation metabolic signature” (PMS), composed of 158 genes (87 upregulated and 71 downregulated gene sets), where 143 are common to all proliferative cells but 15 are cancer specific. Intriguingly, the PMS gene set is enriched for genes encoding rate-limiting enzymes, and its upregulated set with genes associated with poor patient outcome and essential genes. Among these essential genes is ribulose-5-phosphate-3-epimerase (RPE), which encodes a pentose phosphate pathway enzyme and whose role in cancer is still unclear. Collectively, we identified a set of metabolic genes that can serve as novel cancer biomarkers and potential targets for drug development.
Highlights
Recent advances in cancer research have demonstrated the remarkable complexity of this disease [1]
Pearson correlation between mouse and human metabolic gene expression (Figure S1a) demonstrated a statistically significant (p < 0.001, Mann–Whitney U test) high correlation between samples derived from the same tissue relative to the comparison with other tissues (Figure S1b)
This enzyme converts 5-phospho-α-D-ribose 1-diphosphate (PRPP) into 5-phospho-β-D-ribosyl-amine (PRA) through the use of glutamine as an amine donor (Figure 5). This pathway ends with the generation of inosine monophosphate (IMP) that is the precursor for adenosine monophosphate (AMP) and guanosine monophosphate (GMP) synthesis
Summary
Recent advances in cancer research have demonstrated the remarkable complexity of this disease [1]. These subtypes can be categorized by the expression of selective markers that, in many instances, have a definite effect on the patient outcomes [3] Despite this complexity and heterogeneity, about 20 years ago, a series of shared hallmarks that broadly describes the biology of cancer was proposed [4] and refined a decade later [5]. The “Warburg effect” defines the glycolysis pathway as the preferred mechanism for cancer cells to generate ATP [9], rather than the more efficient mitochondrial oxidative phosphorylation pathway [10] These early findings promoted extensive research over the years, expanding our understanding of cancer-dependent metabolic rewiring
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
