Fueling Neuroblastoma: Genomic Analysis of Ketolytic and Glycolytic Gene
Expression in Relation to MYCN Oncogene Amplification, Stage, and
Prognosis
Abstract
Background Neuroblastoma (NB) is a childhood cancer of the sympathetic
nervous system, and its prognosis is poor. NB undergoes transcription
changes to use aerobic glycolysis as its primary metabolic pathway.
Aerobic glycolysis provides an immediate source of ATP in metastasis
proliferation, and therefore may be exploited in dietary therapies, such
as the ketone diet. Procedure In this study, the expression of
glycolytic and ketolytic genes in the context of MYCN oncogene
amplification, tumor staging, and Kaplan-Meier survivability was
investigated using the R2: Genomics analysis and visualisation platform
(http://r2.amc.nl). The R2 database is a platform for gene expression
and prognostic data for primary tumour samples. Six NB genomics datasets
were accessed and further analysed in GraphPad Prism to investigate the
relationships between glycolytic and ketolytic gene expression and
prognosis. Results Glycolytic gene expression is increased in
MYCN amplified, metastatic tumours, and is associated with worse
event free survival. Ketolytic gene expression is lower in metastatic
tumours and is associated with better event free survivability. The
glycolytic gene expression profile of NB suggests that elevated levels
correlate with tumorigenicity and low probability of survival. Ketolytic
gene expression patterns suggest a decreased reliance for ketolytic
energy, which may be exploited to slow tumorigenic growth. Conclusions
This study validates the glycolytic gene expression profiles in
metastatic and MYCN-amplified NB tumours and suggest the potential use
of these genes in prognosis prediction. Furthermore, the study
highlights the reliability and utility of the R2 database as an
oncogenomic tool for NB research.