hsa-miR-9 and drug control over the P38 network as driving disease outcome in GBM patients

Abstract

Introduction: Glioblastoma multiforme (GBM) is the most common and lethal primary tumor of the brain and is associated with one of the worst 5-year survival rates among all human cancers. Identification of key molecular interactions and genetic variations that influence disease course and patient outcome may provide important insights into disease biology and treatment. Results: The P38 network and the micro RNA hsa-miR-9 significantly correlate with patient outcome in a manner that suggests a possible control mechanism of the microRNA over the pathway. This control mechanism can possibly be mimicked by a set of drugs that target the P38 pathway. These drugs are part of the treatment regimen for a subpopulation of the patients that participated in the TCGA study and for which the study provides clinical information. Conclusions: The results presented here call for attention to P38 network targeted treatments and identify the P38 network–hsa-miR-9 interaction as a critical control mechanism in GBM. Methods The Cancer Genome Atlas (TCGA), http://cancergenome.nih.gov/, provides the molecular profiles of 373 patients. Using the TCGA data set and two additional independent molecular and clinical data sets with a set of network-based computational algorithms, we were able to identify a single pathway and a microRNA that were implicated with disease outcome.