Skip to Main content Skip to Navigation
Journal articles

A 4-gene signature associated with clinical outcome in high-grade gliomas.

Abstract : PURPOSE: Gene expression studies provide molecular insights improving the classification of patients with high-grade gliomas. We have developed a risk estimation strategy based on a combined analysis of gene expression data to search for robust biomarkers associated with outcome in these tumors. EXPERIMENTAL DESIGN: We performed a meta-analysis using 3 publicly available malignant gliomas microarray data sets (267 patients) to define the genes related to both glioma malignancy and patient outcome. These biomarkers were used to construct a risk-score equation based on a Cox proportional hazards model on a subset of 144 patients. External validations were performed on microarray data (59 patients) and on RT-qPCR data (194 patients). The risk-score model performances (discrimination and calibration) were evaluated and compared with that of clinical risk factors, MGMT promoter methylation status, and IDH1 mutational status. RESULTS: This interstudy cross-validation approach allowed the identification of a 4-gene signature highly correlated to survival (CHAF1B, PDLIM4, EDNRB, and HJURP), from which an optimal survival model was built (P < 0.001 in training and validation sets). Multivariate analysis showed that the 4-gene risk score was strongly and independently associated with survival (hazard ratio = 0.46; 95% CI, 0.26-0.81; P = 0.007). Performance estimations indicated that this score added beyond standard clinical parameters and beyond both the MGMT methylation status and the IDH1 mutational status in terms of discrimination (C statistics, 0.827 versus 0.835; P < 0.001). CONCLUSION: The 4-gene signature provides an independent risk score strongly associated with outcome of patients with high-grade gliomas.
Complete list of metadatas

https://www.hal.inserm.fr/inserm-00545436
Contributor : Hervé de Villemeur <>
Submitted on : Friday, December 10, 2010 - 11:07:45 AM
Last modification on : Wednesday, December 19, 2018 - 3:02:05 PM

Links full text

Identifiers

Citation

Marie de Tayrac, Marc Aubry, Stephan Saïkali, Amandine Etcheverry, Cyrille Surbled, et al.. A 4-gene signature associated with clinical outcome in high-grade gliomas.. Clinical Cancer Research, American Association for Cancer Research, 2011, 17 (2), pp.317-27. ⟨10.1158/1078-0432.CCR-10-1126⟩. ⟨inserm-00545436⟩

Share

Metrics

Record views

187