Glioblastoma Multiforme is one of the most aggressive and deadly forms of brain cancer. It is known that radiation therapy in some cases causes a higher probability for recurrence or future growth of Glioblastoma Multiforme tumors.
Researchers at the University of Alabama in Birmingham and the University of Chicago have been able to determine what genes are responsible for the phenomena of radiation resistant tumors and hope to develop better treatments as a result of this knowledge.
The research was presented at the Public Library of Science web site on January 5, 2012.
Abstract
Previous reports have implicated an induction of genes in IFN/STAT1 (Interferon/STAT1) signaling in radiation resistant and prosurvival tumor phenotypes in a number of cancer cell lines, and we have hypothesized that upregulation of these genes may be predictive of poor survival outcome and/or treatment response in Glioblastoma Multiforme (GBM) patients. We have developed a list of 8 genes related to IFN/STAT1 that we hypothesize to be predictive of poor survival in GBM patients. Our working hypothesis that over-expression of this gene signature predicts poor survival outcome in GBM patients was confirmed, and in addition, it was demonstrated that the survival model was highly subtype-dependent, with strong dependence in the Proneural subtype and no detected dependence in the Classical and Mesenchymal subtypes. We developed a specific multi-gene survival model for the Proneural subtype in the TCGA (the Cancer Genome Atlas) discovery set which we have validated in the TCGA validation set. In addition, we have performed network analysis in the form of Bayesian Network discovery and Ingenuity Pathway Analysis to further dissect the underlying biology of this gene signature in the etiology of GBM. We theorize that the strong predictive value of the IFN/STAT1 gene signature in the Proneural subtype may be due to chemotherapy and/or radiation resistance induced through prolonged constitutive signaling of these genes during the course of the illness. The results of this study have implications both for better prediction models for survival outcome in GBM and for improved understanding of the underlying subtype-specific molecular mechanisms for GBM tumor progression and treatment response.
Paper
Authors
Christine W. Duarte1*, Christopher D. Willey2, Degui Zhi1, Xiangqin Cui1, Jacqueline J. Harris1, Laura Kelly Vaughan1, Tapan Mehta1, Raymond O. McCubrey1, Nikolai N. Khodarev4, Ralph R. Weichselbaum4, G. Yancey Gillespie3
1 Department of Biostatistics (Section on Statistical Genetics), University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 2 Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 3 Department of Surgery (Neurosurgery), University of Alabama at Birmingham, Birmingham, Alabama, United States of America, 4 Department of Radiation & Cellular Oncology, Ludwig Center for Metastasis Research, University of Chicago, Chicago, Illinois, United States of America
Citation: Duarte CW, Willey CD, Zhi D, Cui X, Harris JJ, et al. (2012) Expression Signature of IFN/STAT1 Signaling Genes Predicts Poor Survival Outcome in Glioblastoma Multiforme in a Subtype-Specific Manner. PLoS ONE 7(1): e29653. doi:10.1371/journal.pone.0029653
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