Prognostic relevance of cytochrome C oxidase in primary glioblastoma multiforme

Patients with primary glioblastoma multiforme (GBM) have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO) promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity i...

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Bibliographic Details
Published in:PloS one 2013-04, Vol.8 (4), p.e61035
Main Authors: Griguer, Corinne E, Cantor, Alan B, Fathallah-Shaykh, Hassan M, Gillespie, G Yancey, Gordon, Amber S, Markert, James M, Radovanovic, Ivan, Clement-Schatlo, Virginie, Shannon, Chevis N, Oliva, Claudia R
Format: Article
Language:English
Subjects:
Analysis
Base Sequence
Biology
Biomarkers
Brain cancer
Brain Neoplasms - enzymology
Brain tumors
Cancer patients
Cancer therapies
Chemotherapy
Cytochrome
Cytochrome c
Cytochrome oxidase
Cytochrome-c oxidase
Deoxyribonucleic acid
Development and progression
DNA
DNA Methylation
DNA Primers
Electron Transport Complex IV - metabolism
Enzymes
Glioblastoma
Glioblastoma - enzymology
Glioblastoma multiforme
Glioblastomas
Glioma
Glycolysis
Health aspects
Humans
Medical research
Medicine
Metabolism
Mitochondria
Mitochondrial DNA
Neurosurgery
Oxidase
Oxidation
Patients
Physiological aspects
Polymerase Chain Reaction
Potassium
Prognosis
Quality
Radiation therapy
Regression analysis
Regression models
Retrospective Studies
Spectrophotometry
Surgery
Survival
Survival Analysis
Tumors
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Summary:Patients with primary glioblastoma multiforme (GBM) have one of the lowest overall survival rates among cancer patients, and reliable biomarkers are necessary to predict patient outcome. Cytochrome c oxidase (CcO) promotes the switch from glycolytic to OXPHOS metabolism, and increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure. Thus, we investigated the relationship between tumor CcO activity and the survival of patients diagnosed with primary GBM. A total of 84 patients with grade IV glioma were evaluated in this retrospective cohort study. Cumulative survival was calculated by the Kaplan-Meier method and analyzed by the log-rank test, and univariate and multivariate analyses were performed with the Cox regression model. Mitochondrial CcO activity was determined by spectrophotometrically measuring the oxidation of cytochrome c. High CcO activity was detected in a subset of glioma tumors (∼30%), and was an independent prognostic factor for shorter progression-free survival and overall survival [P = 0.0087 by the log-rank test, hazard ratio = 3.57 for progression-free survival; P
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0061035