Dataset Information

Identification of a cullin5-RING E3 ligase transcriptome signature in glioblastoma multiforme.

ABSTRACT: Glioblastoma multiforme (GBM) is the deadliest type of brain tumor. The median survival time for patients with GBM is only 15 months, even following maximal surgical resection and chemotherapy and radiation therapy. A genetic biomarker could enable a paradigm shift in precise diagnosis, personalized therapeutics and prognosis. In this study, we employed the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, and the Ivy Glioblastoma Atlas Project databases for RNA sequencing (RNA-seq) analysis and clinicopathological studies. We demonstrated that elevated expression of the RNF7, TCEB1, SOCS1 and SOCS3 genes, which encode components of cullin5-RING E3 ligase (CRL5), predict unfavorable GBM prognoses. In GBM and glioma cases carrying IDH1 mutations, SOCS1 and SOCS3 methylation was increased and their expression was downregulated. This study has thus identified a simple transcriptome signature for GBM prognosis.

SUBMITTER: Zheng S

PROVIDER: S-EPMC7521521 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Identification of a cullin5-RING E3 ligase transcriptome signature in glioblastoma multiforme.

Zheng Shuhua S Li Zhenhao Z

Aging 20200914 17

Glioblastoma multiforme (GBM) is the deadliest type of brain tumor. The median survival time for patients with GBM is only 15 months, even following maximal surgical resection and chemotherapy and radiation therapy. A genetic biomarker could enable a paradigm shift in precise diagnosis, personalized therapeutics and prognosis. In this study, we employed the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, and the Ivy Glioblastoma Atlas Project databases for RNA sequencing (RNA-seq) analysis ...[more]

PMID: 32931454

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Project description: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 < 0.001) in the training dataset. Similar result was observed in the test dataset (median 11.40 vs. 16.80 months, log-rank test P = 0.001) and the independent set (median 8.93 vs. 16.22 months, log-rank test P = 0.007). Multivariable Cox regression analysis verified that it was an independent prognostic factor for the postsurgical patients with GBM. Compared with IDH mutation status, O-(6)-methylguanine DNA methyltransferase promoter methylation status and age, the signature was proved to have a superior predictive power. And stratified analysis found that the signature could further separated postoperative GBM patients who received TMZ-chemoradiation into high- and low-risk groups in TCGA and GEO dataset. CONCLUSIONS:The PCG-lncRNA signature was a novel prognostic marker to predict survival and TMZ-chemoradiation response in GBM patients after surgery.

Dataset Information

Identification of a cullin5-RING E3 ligase transcriptome signature in glioblastoma multiforme.

Publications

Identification of a cullin5-RING E3 ligase transcriptome signature in glioblastoma multiforme.

Similar Datasets

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