A transcription network at the core of brain cancer

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Research published this week in Genome Medicine provides new insights
into the molecular pathways underlying brain cancer (glioblastoma multiforme). Sol
Efroni
and Rotem Ben-Hamo from Bar IIan University in Israel analyzed gene
expression and clinical data for a large number of patients, with the aim of
identifying prognostic biomarkers and new therapeutic targets.

Glioblastoma multiforme is a common,
aggressive form of brain cancer associated with extremely low survival rates. The
disease is usually fatal even following therapy, highlighting the need for
early diagnosis and the development of more effective drug regimes. In this
study, Efroni and Ben-Hamo applie
d a series of computational algorithms to five
independent microarray datasets to identify gene expression networks that
correlate with poor pro
gnosis. As part of their analysis, data from The Cancer
Genome Atlas (TCGA), Gene Expression Omnibus (GEO) database and The National
Cancer Institute’s Pathway Interaction Database (PID) were merged, representing
a uniquely powerful “systems biology” approach to biomarker discovery.

 

This integrated approach revealed that the
expression of one pathway, the p38/MAPK transcription network, significantly
affiliates with poor survival. This network was shown to be regulated by a
microRNA, hsa-miR-9, implicating another important biomarker for the disease.
Interestingly, analysis of DrugBank data showed that patients who had received
drugs targeting the p38/MAPK pathway displayed higher survival rates compared
with patients who had been treated with other drugs. These results suggest that
the p38/MAPK network is critical in glioblastoma multiforme progression and
should form the focus of future clinical studies of the disease.