A biology-driven approach identifies the hypoxia gene signature as a predictor of the outcome of neuroblastoma patients.

Molecular Cancer
Paolo FardinLuigi Varesio

Abstract

Hypoxia is a condition of low oxygen tension occurring in the tumor microenvironment and it is related to poor prognosis in human cancer. To examine the relationship between hypoxia and neuroblastoma, we generated and tested an in vitro derived hypoxia gene signature for its ability to predict patients' outcome. We obtained the gene expression profile of 11 hypoxic neuroblastoma cell lines and we derived a robust 62 probesets signature (NB-hypo) taking advantage of the strong discriminating power of the l1-l2 feature selection technique combined with the analysis of differential gene expression. We profiled gene expression of the tumors of 88 neuroblastoma patients and divided them according to the NB-hypo expression values by K-means clustering. The NB-hypo successfully stratifies the neuroblastoma patients into good and poor prognosis groups. Multivariate Cox analysis revealed that the NB-hypo is a significant independent predictor after controlling for commonly used risk factors including the amplification of MYCN oncogene. NB-hypo increases the resolution of the MYCN stratification by dividing patients with MYCN not amplified tumors in good and poor outcome suggesting that hypoxia is associated with the aggressiveness of ne...Continue Reading

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Jul 17, 2013·BMC Bioinformatics·Davide CangelosiLuigi Varesio
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Datasets Mentioned

BETA
GSE17714

Methods Mentioned

BETA
electrophoresis
chip

Software Mentioned

Cluster
NB
R package
Affymetrix Microarray Suite
StatPlus
R scripts
Affymetrix
Prism
TreeView
MATLAB

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