Dataset Information

Clinical significance of FBXO17 gene expression in high-grade glioma.

ABSTRACT:

Background

High-grade gliomas (HGGs) exhibit marked heterogeneity in clinical behavior. The purpose of this study was to identify a novel biomarker that predicts patient outcome, which is helpful in HGG patient management.

Methods

We analyzed gene expression profiles of 833 HGG cases, representing the largest patient population ever reported. Using the data set from the Cancer Genome Atlas (TCGA) and random partitioning approach, we performed Cox proportional hazards model analysis to identify novel prognostic mRNAs in HGG. The predictive capability was further assessed via multivariate analysis and validated in 4 additional data sets. The Kaplan-Meier method was used to evaluate survival difference between dichotomic groups of patients. Correlation of gene expression and DNA methylation was evaluated via Student's t-test.

Results

Patients with elevated FBXO17 expression had a significantly shorter overall survival (OS) (P?=?0.0011). After adjustment by IDH1 mutation, sex, and patient age, FBXO17 gene expression was significantly associated with OS (HR?=?1.29, 95% CI =1.04-1.59, P?=?0.018). In addition, FBXO17 expression can significantly distinguish patients by OS not only among patients who received temozolomide chemotherapy (HR 1.35, 95% CI =1.12-1.64, P?=?0.002) but also among those who did not (HR?=?1.48, 95% CI =1.20-1.82, P?ConclusionEpigenetically modulated FBXO17 has a potential as a stratification factor for clinical decision-making in HGG.

SUBMITTER: Du D

PROVIDER: S-EPMC6069786 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Clinical significance of FBXO17 gene expression in high-grade glioma.

Du Di D Yuan Jian J Ma Wencai W Ning Jing J Weinstein John N JN Yuan Xianrui X Fuller Greg N GN Liu Yuexin Y

BMC cancer 20180731 1

<h4>Background</h4>High-grade gliomas (HGGs) exhibit marked heterogeneity in clinical behavior. The purpose of this study was to identify a novel biomarker that predicts patient outcome, which is helpful in HGG patient management.<h4>Methods</h4>We analyzed gene expression profiles of 833 HGG cases, representing the largest patient population ever reported. Using the data set from the Cancer Genome Atlas (TCGA) and random partitioning approach, we performed Cox proportional hazards model analysi ...[more]

PMID: 30064493

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Project description:IntroductionPatients with high-grade glioma (HGG) suffered poor survival due to inherent or acquired therapeutic resistance and refractory recurrence. The outcome of HGG patients has improved little during the past decade. Therefore, molecular signatures are urgently needed for improving diagnosis, survival prediction and identification of therapeutic targets for HGG. E2F transcription factors (E2Fs), a family of transcription factors recognized as master regulators of cell proliferation, have been found to be involved in the pathogenesis of various tumor types.AimsTo investigate the expression of E2Fs and their prognosis value in high-grade glioma (HGG).ResultsExpression of E2Fs was analyzed in 394 HGG samples from TCGA dataset. E2Fs were generally expressed in HGG. Except for E2F3 and E2F5, expression of E2Fs was significantly upregulated and linked with grade progression. E2F1, E2F2, E2F7, and E2F8 were highly correlated with aggressive proliferation oncogenes, as well as potential therapeutic resistance oncogenes. Elevated E2Fs (not E2F3) were associated with adverse tumor features and poorer outcome. E2F7 and E2F8 exhibited superior outcome prediction performance compared with other E2Fs. Additionally, E2F7 and E2F8 independently predicted poorer survival in HGG patients. Gene set enrichment analysis identified a variety of critical oncogenic pathways that were tightly associated with E2F7 or E2F8, including epithelial-mesenchymal transition, NFκB, STAT3, angiogenesis pathways. Furthermore, elevated expression of E2F7 indicated worse therapeutic response of HGG to irradiation and silencing of E2F7 conferred higher cell-killing effect when combined with irradiation treatment. Mechanically, E2F7 directly regulates the transcriptional activity of EZH2 via binding at the corresponding promoter area.ConclusionsE2Fs (except for E2F3 and E2F5) are highly expressed in HGG and indicate adverse outcome. E2F7 and E2F8 were identified as novel potential prognostic markers in HGG. E2F7 was further validated to be closely associated with radioresistance of HGG and a critical transcriptional regulator of EZH2.

Dataset Information

Clinical significance of FBXO17 gene expression in high-grade glioma.

Background

Methods

Results

Publications

Clinical significance of FBXO17 gene expression in high-grade glioma.

Similar Datasets

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