Gene Expression Profiling And Graphical Association in Glioblastoma Survival
Abstract
Despite the strikingly grave prognosis for older patients with glioblastomas, significant variability in patient outcome is experienced. To explore the potential for developing improved prognostic capabilities based on the elucidation of potential biological relationships, we performed analyses of genes commonly mutated, amplified, or deleted in glioblastomas and DNA microarray gene expression data from tumors of glioblastoma patients of age greater than 50 for whom survival is known. No prognostic significance was associated with genetic changes in EGFR (amplified in 17 of 41 patients), TP53 (mutated in 11 of 41 patients), p16INK4A (deleted in 15 of 33 patients) or PTEN (mutated in 15 of 41 patients). Statistical analysis of the gene expression data in connection with survival involved exploration of regression models on small subsets of genes, based on computational search over multiple regression models with cross-validation to assess predictive validity. The analysis generated a set of regression models that, when weighted and combined according to posterior probabilities implied by the statistical analysis, identify patterns in expression of a small subset of genes that are associated with survival and have value in assessing survival risks. The dominant genes across multiple such regression models involve three key genes SPARC (Osteonectin), Doublecortex and Semaphorin3B that play roles in cellular migration processes. Additional analysis, based on statistical graphical association models constructed using similar computational analysis methods, reveals others genes that support the view that multiple mediators of tumor invasion may be important prognostic factors in glioblastomas in older patients.
Authors
Jeremy N. Rich, Chris Hans, Beatrix Jones, Edwin S. Iversen, Roger E. McClendon, B. K. Ahmed Rasheed, Adrian Dobra, Holly K. Dressman, Darell D. Bigner, Joe R. Nevins and Mike West
Contact
- Mike West (mw@stat.duke.edu)