Perry, Christina, Agarwal, Devika 
ORCID: 0000-0002-5203-307X, Abdel-Fatah, Tarek MA, Lourdusamy, Anbarasu ORCID: 0000-0002-1978-6301, Grundy, Richard, Auer, Dorothee T ORCID: 0000-0002-4745-3635, Walker, David, Lakhani, Ravi, Scott, Ian S ORCID: 0000-0003-1266-9521, Chan, Stephen et al (show 2 more authors)
(2014)
Dissecting DNA repair in adult high grade gliomas for patient stratification in the post-genomic era.
Oncotarget, 5 (14).
pp. 5764-5781.
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Abstract
Deregulation of multiple DNA repair pathways may contribute to aggressive biology and therapy resistance in gliomas. We evaluated transcript levels of 157 genes involved in DNA repair in an adult glioblastoma Test set (n=191) and validated in 'The Cancer Genome Atlas' (TCGA) cohort (n=508). A DNA repair prognostic index model was generated. Artificial neural network analysis (ANN) was conducted to investigate global gene interactions. Protein expression by immunohistochemistry was conducted in 61 tumours. A fourteen DNA repair gene expression panel was associated with poor survival in Test and TCGA cohorts. A Cox multivariate model revealed APE1, NBN, PMS2, MGMT and PTEN as independently associated with poor prognosis. A DNA repair prognostic index incorporating APE1, NBN, PMS2, MGMT and PTEN stratified patients in to three prognostic sub-groups with worsening survival. APE1, NBN, PMS2, MGMT and PTEN also have predictive significance in patients who received chemotherapy and/or radiotherapy. ANN analysis of APE1, NBN, PMS2, MGMT and PTEN revealed interactions with genes involved in transcription, hypoxia and metabolic regulation. At the protein level, low APE1 (p=0.031) and low PTEN (p=0.042) remain associated with poor prognosis. In conclusion, multiple DNA repair pathways operate to influence biology and clinical outcomes in adult high grade gliomas.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Glioblastoma, Brain Neoplasms, Survival Analysis, Genomics, DNA Repair, Gene Expression, Adolescent, Adult, Aged, Aged, 80 and over, Middle Aged, Female, Male, Young Adult, Biomarkers, Tumor |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 18 Dec 2023 08:52 |
| Last Modified: | 18 Mar 2024 04:10 |
| DOI: | 10.18632/oncotarget.2180 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3177461 |
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