Reverse engineering the neuroblastoma regulatory network uncovers MAX as one of the master regulators of tumor progression

PloS One
Ricardo D'Oliveira AlbanusJosé Cláudio Fonseca Moreira

Abstract

Neuroblastoma is the most common extracranial tumor and a major cause of infant cancer mortality worldwide. Despite its importance, little is known about its molecular mechanisms. A striking feature of this tumor is its clinical heterogeneity. Possible outcomes range from aggressive invasion to other tissues, causing patient death, to spontaneous disease regression or differentiation into benign ganglioneuromas. Several efforts have been made in order to find tumor progression markers. In this work, we have reconstructed the neuroblastoma regulatory network using an information-theoretic approach in order to find genes involved in tumor progression and that could be used as outcome predictors or as therapeutic targets. We have queried the reconstructed neuroblastoma regulatory network using an aggressive neuroblastoma metastasis gene signature in order to find its master regulators (MRs). MRs expression profiles were then investigated in other neuroblastoma datasets so as to detect possible clinical significance. Our analysis pointed MAX as one of the MRs of neuroblastoma progression. We have found that higher MAX expression correlated with favorable patient outcomes. We have also found that MAX expression and protein levels we...Continue Reading

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Citations

Jan 16, 2016·Cancers·Laura L Stafman, Elizabeth A Beierle
Dec 4, 2014·Molecular Neurobiology·Matheus Augusto de Bittencourt PasqualiJosé Cláudio Fonseca Moreira
Jan 27, 2018·Cell Death & Disease·Kadri ValterVladimir Gogvadze
Dec 29, 2020·The Journal of Clinical Endocrinology and Metabolism·Amanda J SeabrookEmma L Duncan

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Datasets Mentioned

BETA
GSE3996
GSE16476

Methods Mentioned

BETA
surgical resection
biopsies

Software Mentioned

Kaplan
Meier Plotter
R
RTN
JetSet
Survcomp
Limma R package
FIMO
Survival

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