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Gene Expression Profiling and Genetic Markers in Glioblastoma Survival
- Source :
- Cancer Research. 65:4051-4058
- Publication Year :
- 2005
- Publisher :
- American Association for Cancer Research (AACR), 2005.
-
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 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.
- Subjects :
- Doublecortin Domain Proteins
Genetic Markers
Male
Cancer Research
Loss of Heterozygosity
Semaphorins
Computational biology
Bioinformatics
Gene expression
Humans
Tensin
Osteonectin
Epidermal growth factor receptor
Survival rate
Gene
Cyclin-Dependent Kinase Inhibitor p16
Aged
Membrane Glycoproteins
biology
Brain Neoplasms
Gene Expression Profiling
Tumor Suppressor Proteins
Neuropeptides
PTEN Phosphohydrolase
Reproducibility of Results
Middle Aged
Phosphoric Monoester Hydrolases
ErbB Receptors
Survival Rate
Gene expression profiling
Oncology
Genetic marker
biology.protein
Female
Tumor Suppressor Protein p53
DNA microarray
Glioblastoma
Microtubule-Associated Proteins
Subjects
Details
- ISSN :
- 15387445 and 00085472
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Cancer Research
- Accession number :
- edsair.doi.dedup.....a574f9c5ac27651f4cbd2850346d81cf