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Identification of a multidimensional transcriptome signature for survival prediction of postoperative glioblastoma multiforme patients.

ABSTRACT: BACKGROUND:Glioblastoma multiform (GBM) is a devastating brain tumor with maximum surgical resection, radiotherapy plus concomitant and adjuvant temozolomide (TMZ) as the standard treatment. Diverse clinicopathological and molecular features are major obstacles to accurate predict survival and evaluate the efficacy of chemotherapy or radiotherapy. Reliable prognostic biomarkers are urgently needed for postoperative GBM patients. METHODS:The protein coding genes (PCGs) and long non-coding RNA (lncRNA) gene expression profiles of 233 GBM postoperative patients were obtained from The Cancer Genome Atlas (TCGA), TANRIC and Gene Expression Omnibus (GEO) database. We randomly divided the TCGA set into a training (n?=?76) and a test set (n?=?77) and used GSE7696 (n?=?80) as an independent validation set. Survival analysis and the random survival forest algorithm were performed to screen survival associated signature. RESULTS:Six PCGs (EIF2AK3, EPRS, GALE, GUCY2C, MTHFD2, RNF212) and five lncRNAs (CTD-2140B24.6, LINC02015, AC068888.1, CERNA1, LINC00618) were screened out by a risk score model and formed a PCG-lncRNA signature for its predictive power was strongest (AUC?=?0.78 in the training dataset). The PCG-lncRNA signature could divide patients into high- risk or low-risk group with significantly different survival (median 7.47 vs. 18.27 months, log-rank test P?

SUBMITTER: Gao WZ

PROVIDER: S-EPMC6302404 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Project description:ObjectivesThis study aimed to establish and validate a prognostic model based on magnetic resonance imaging and clinical features to predict the survival time of patients with glioblastoma multiforme (GBM).MethodsIn this study, a convolutional denoising autoencoder (DAE) network combined with the loss function of the Cox proportional hazard regression model was used to extract features for survival prediction. In addition, the Kaplan-Meier curve, the Schoenfeld residual analysis, the time-dependent receiver operating characteristic curve, the nomogram, and the calibration curve were performed to assess the survival prediction ability.ResultsThe concordance index (C-index) of the survival prediction model, which combines the DAE and the Cox proportional hazard regression model, reached 0.78 in the training set, 0.75 in the validation set, and 0.74 in the test set. Patients were divided into high- and low-risk groups based on the median prognostic index (PI). Kaplan-Meier curve was used for survival analysis (p = < 2e-16 in the training set, p = 3e-04 in the validation set, and p = 0.007 in the test set), which showed that the survival probability of different groups was significantly different, and the PI of the network played an influential role in the prediction of survival probability. In the residual verification of the PI, the fitting curve of the scatter plot was roughly parallel to the x-axis, and the p-value of the test was 0.11, proving that the PI and survival time were independent of each other and the survival prediction ability of the PI was less affected than survival time. The areas under the curve of the training set were 0.843, 0.871, 0.903, and 0.941; those of the validation set were 0.687, 0.895, 1.000, and 0.967; and those of the test set were 0.757, 0.852, 0.683, and 0.898.ConclusionThe survival prediction model, which combines the DAE and the Cox proportional hazard regression model, can effectively predict the prognosis of patients with GBM.

Project description:BackgroundBrain glioblastoma multiforme (GBM) is the most common primary malignant intracranial tumor. The prognosis of this disease is extremely poor. While the introduction of β-interferon (IFN-β) regimen in the treatment of gliomas has significantly improved the outcome of patients; The mechanism by which IFN-β induces increased TMZ sensitivity has not been described. Therefore, the main objective of the study was to elucidate the molecular mechanisms responsible for the beneficial effect of IFNβ in GBM.MethodsMessenger RNA expression profiles and clinicopathological data were downloaded from The Cancer Genome Atlas (TCGA) GBM and GSE83300 dataset from the Gene Expression Omnibus. Univariate Cox regression analysis and lasso Cox regression model established a novel 4-gene IFN-β signature (peroxiredoxin 1, Sec61 subunit beta, X-ray repair cross-complementing 5, and Bcl-2-like protein 2) for GBM prognosis prediction. Further, GBM samples (n=50) and normal brain tissues (n=50) were then used for real-time polymerase chain reaction experiments. Gene set enrichment analysis (GSEA) was performed to further understand the underlying molecular mechanisms. Pearson correlation was applied to calculate the correlation between the long non-coding RNAs (lncRNAs) and IFN-β-associated genes. An lncRNA with a correlation coefficient |R2|>0.3 and P<0.05 was considered to be an IFN-β-associated lncRNA.ResultsPatients in the high-risk group had significantly poorer survival than patients in the low-risk group. The signature was found to be an independent prognostic factor for GBM survival. Furthermore, GSEA revealed several significantly enriched pathways, which might help explain the underlying mechanisms. Our study identified a novel robust 4-gene IFN-β signature for GBM prognosis prediction. The signature might contain potential biomarkers for metabolic therapy and treatment response prediction for GBM patients.ConclusionsIn the present study, we established a novel IFN-β-associated gene signature to predict the overall survival of GBM patients, which may help in clinical decision making for individual treatment.

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Identification of a multidimensional transcriptome signature for survival prediction of postoperative glioblastoma multiforme patients.

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