Dataset Information

Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma.

ABSTRACT:

Background

We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of TERT mutation, EGFR amplification, and CDKN2A/B deletion on isocitrate dehydrogenase (IDH)-wildtype GBM.

Methods

IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without histological features of GBM but with one of the following molecular alterations: TERT mutation, EGFR amplification, or combination of whole chromosome 7 gain and whole chromosome 10 loss. Overall survival (OS) and progression-free survival (PFS) were calculated from RT and analyzed using the Kaplan-Meier method. Multivariable analysis (MVA) was performed using Cox regression to identify independent predictors of OS and PFS.

Results

Of the 367 eligible patients, the median follow-up was 11.7 months. mGBM and hGBM did not have significantly different OS (median: 16.6 vs 13.5 months, respectively, P = .16), nor PFS (median: 11.7 vs 7.3 months, respectively, P = .08). However, mGBM was associated with better OS (hazard ratio [HR] 0.50, 95% CI 0.29-0.88) and PFS (HR 0.43, 95% CI 0.26-0.72) than hGBM after adjusting for known prognostic factors on MVA. CDKN2A/B deletion was associated with worse OS (HR 1.57, 95% CI 1.003-2.46) and PFS (HR 1.57, 95% CI 1.04-2.36) on MVA, but TERT mutation and EGFR amplification were not.

Conclusion

Criteria for mGBM may require further refinement and validation. CDKN2A/B deletion, but not TERT mutation or EGFR amplification, may be an independent prognostic biomarker for IDH-wildtype GBM patients.

SUBMITTER: Ma S

PROVIDER: S-EPMC7668466 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma.

Ma Sirui S Rudra Soumon S Campian Jian L JL Dahiya Sonika S Dunn Gavin P GP Johanns Tanner T Goldstein Michael M Kim Albert H AH Huang Jiayi J

Neuro-oncology advances 20200101 1

<h4>Background</h4>We aimed to evaluate the clinical outcomes of molecular glioblastoma (mGBM) as compared to histological GBM (hGBM) and to determine the prognostic impact of <i>TERT</i> mutation, <i>EGFR</i> amplification, and <i>CDKN2A/B</i> deletion on isocitrate dehydrogenase (IDH)-wildtype GBM.<h4>Methods</h4>IDH-wildtype GBM patients treated with radiation therapy (RT) between 2012 and 2019 were retrospectively analyzed. mGBM was defined as grade II-III IDH-wildtype astrocytoma without hi ...[more]

PMID: 33235995

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Project description:Objectives: In the present study, we aimed to determine the candidate genes that may function as biomarkers to further distinguish patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM), which are heterogeneous with respect to clinical outcomes. Materials and Methods: We selected 41 candidate genes associated with overall survival (OS) using univariate Cox regression from IDH-wildtype GBM patients based on RNA sequencing (RNAseq) expression data from the Chinese Glioma Genome Atlas (CGGA, n = 105) and The Cancer Genome Atlas (TCGA, n = 139) cohorts. Next, a seven-gene-based risk signature was formulated according to Least Absolute Shrinkage and Selection Operator (LASSO) regression algorithm in the CGGA RNAseq database as a training set, while another 525 IDH-wildtype GBM patient TCGA datasets, consisting of RNA sequencing and microarray data, were used for validation. Patient survival in the low- and high-risk groups was calculated using Kaplan-Meier survival curve analysis and the log-rank test. Uni-and multivariate Cox regression analysis was used to assess the prognosis value. Gene oncology (GO) and gene set enrichment analysis (GSEA) were performed for the functional analysis of the seven-gene-based risk signature. Results: We developed a seven-gene-based signature, which allocated each patient to a risk group (low or high). Patients in the high-risk group had dramatically shorter overall survival than their low-risk counterparts in three independent cohorts. Univariate and multivariate analysis showed that the seven-gene signature remained an independent prognostic factor. Moreover, the seven-gene risk signature exhibited a striking prognostic validity, with AUC of 78.4 and 73.9%, which was higher than for traditional "age" (53.7%, 62.4%) and "GBM sub-type" (57.7%, 52.9%) in the CGGA- and TCGA-RNAseq databases, respectively. Subsequent bioinformatics analysis predicted that the seven-gene signature was involved in the inflammatory response, immune response, cell adhesion, and apoptotic process. Conclusions: Our findings indicate that the seven-gene signature could be a potential prognostic biomarker. This study refined the current classification system of IDH-wildtype GBM and may provide a novel perspective for the research and individual therapy of IDH-wildtype GBM.

Dataset Information

Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma.

Background

Methods

Results

Conclusion

Publications

Prognostic impact of CDKN2A/B deletion, TERT mutation, and EGFR amplification on histological and molecular IDH-wildtype glioblastoma.

Similar Datasets

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