Abstract
Background: Isocitrate dehydrogenase (IDH) mutations are the most common genetic aberrations in gliomagenesis. We aimed to build a high-efficiency prediction gene signature in patients with IDH-mutant glioma.Methods: In total, 167 gliomas from Chinese Glioma Genome Atlas (CGGA) dataset were included for discovery. The Cancer Genome Atlas (TCGA) dataset was used for validation. R language was the main software environment for our statistical operation and graphics.Results: We applied the Time-Dependent ROC Curve (timeROC) method to estimate the gene prediction accuracy of 3 years and 5 years in two datasets. Seven genes were selected for further analysis (AUC ≥ 0.7 in two datasets). A seven-gene enrichment score was established to predict the overall survival of 3 years and 5 years for IDH- mutant glioma patients. Moreover, the seven-gene signature was an independent prognostic indicator for patients with IDH-mutant glioma. Gene Ontology (GO) Analysis of associated genes revealed signature-related biological process of cell cycle and division.Conclusion: We have identified a seven-gene signature that can provide a more accurate predictor of 3 years and 5 years for patients with IDH-mutant glioma. Moreover, the signature may potentially help neurosurgeons with the clinical personalized management of gliomas.
Highlights
Gliomas, ranging from grade II -IV, are the most common malignant intracranial tumors
According to the 2016 World Health Organization (WHO) Classification based on the mutation status of isocitrate dehydrogenase (IDH) and Chromosome 1p/19q status, the diffuse gliomas are mainly divided into five subtypes, Lower grade gliomas (LGG) with Isocitrate dehydrogenase (IDH)-mutant and 1p/19qcodeleted subtype, LGG with IDH-mutant and 1p/19qintact subtype, LGG with IDH-wildtype subtype, GBM with IDH-mutant subtype, and GBM with IDHwildtype subtype [3]
IDHmutant glioma is an important entity ranging from WHO grade II to grade IV with different clinical manifestations, and objective molecular based classification is in urgent need
Summary
Gliomas, ranging from grade II -IV, are the most common malignant intracranial tumors. We developed a robust prognostic model to predict the overall survival of patients with IDH-mutant glioma. By applying Time-Dependent receiver operating characteristic (timeROC) curve and GSVA method, we ascertained a seven-gene signature as an independent prognostic factor, which could accurately predict the 3 years and 5 years overall survival for patients with IDH-mutant glioma. This robust prognostic model provided a more comprehensive view for patients with IDH-mutant glioma and highlighted its potential role in the clinical management of gliomas. A seven-gene enrichment score was established to predict the overall survival of 3 years and 5 years for IDH- mutant glioma patients. The signature may potentially help neurosurgeons with the clinical personalized management of gliomas
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