Gene expression profiling and genetic markers in glioblastoma survival.
Journal Article (Journal Article)
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 did analyses of genes commonly mutated, amplified, or deleted in glioblastomas and DNA microarray gene expression data from tumors of glioblastoma patients of age >50 for whom survival is known. No prognostic significance was associated with genetic changes in epidermal growth factor receptor (amplified in 17 of 41 patients), TP53 (mutated in 11 of 41 patients), p16INK4A (deleted in 15 of 33 patients), or phosphatase and tensin homologue (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 such multiple regression models involve three key genes-SPARC (Osteonectin), Doublecortex, and Semaphorin3B-which play key roles in cellular migration processes. Additional analysis, based on statistical graphical association models constructed using similar computational analysis methods, reveals other genes which support the view that multiple mediators of tumor invasion may be important prognostic factor in glioblastomas in older patients.
Full Text
Duke Authors
Cited Authors
- Rich, JN; Hans, C; Jones, B; Iversen, ES; McLendon, RE; Rasheed, BKA; Dobra, A; Dressman, HK; Bigner, DD; Nevins, JR; West, M
Published Date
- May 15, 2005
Published In
Volume / Issue
- 65 / 10
Start / End Page
- 4051 - 4058
PubMed ID
- 15899794
International Standard Serial Number (ISSN)
- 0008-5472
Digital Object Identifier (DOI)
- 10.1158/0008-5472.CAN-04-3936
Language
- eng
Conference Location
- United States