Isocitrate Dehydrogenase Mutations in Low-Grade Gliomas Correlate With Prolonged Overall Survival in Older Patients

Jones, Pamela S.; Carroll, Kate; Koch, Matthew J.; DiCesare, Jasmine A T; Reitz, Kara; Frosch, Matthew P.; Barker, Fred G.; Cahill, Daniel P.; Curry, William T.

doi:10.1093/neuros/nyy149

Cited by 7 publications

(7 citation statements)

References 43 publications

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“…Similar results regarding older age and IDH1 mutation were put forward by Jones et al. ( 29 ). A multivariate analysis from Figure 3B indicated that grade III has been shown to lead to an elevated risk when compared with grade II.…”

Section: Discussionsupporting

confidence: 85%

“…The IDH1 mutation was the only protective factor, and the risk of patients with this mutation was 0.464 times that of the patients without this mutation ( Figure 3B). Similar results regarding older age and IDH1 mutation were put forward by Jones et al (29). A multivariate analysis from Figure 3B indicated that grade III has been shown to lead to an elevated risk when compared with grade II.…”

Section: Discussionsupporting

confidence: 83%

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An Immune-Related Signature for Predicting the Prognosis of Lower-Grade Gliomas

Chen

et al. 2020

Front. Immunol.

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BackgroundLower-grade gliomas (LGGs) have more favorable outcomes than glioblastomas; however, LGGs often progress to process glioblastomas within a few years. Numerous studies have proven that the tumor microenvironment (TME) is correlated with the prognosis of glioma.MethodsLGG RNA-Sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) were extracted and then divided into training and testing cohorts, respectively. Immune-related differentially expressed genes (DEGs) were screened to establish a prognostic signature by a multivariate Cox proportional hazards regression model. The immune-related risk score and clinical information, such as age, sex, World Health Organization (WHO) grade, and isocitrate dehydrogenase 1 (IDH1) mutation, were used to independently validate and develop a prognostic nomogram. GO and KEGG pathway analyses to DEGs between immune-related high-risk and low-risk groups were performed.ResultsSixteen immune-related genes were screened for establishing a prognostic signature. The risk score had a negative correlation with prognosis, with an area under the receiver operating characteristic (ROC) curve of 0.941. The risk score, age, grade, and IDH1 mutation were identified as independent prognostic factors in patients with LGGs. The hazard ratios (HRs) of the high-risk score were 5.247 [95% confidence interval (CI) = 3.060–8.996] in the multivariate analysis. A prognostic nomogram of 1-, 3-, and 5-year survival was established and validated internally and externally. Go and KEGG pathway analyses implied that immune-related biological function and pathways were involved in the TME.ConclusionThe immune-related prognostic signature and the prognostic nomogram could accurately predict survival.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 83%

An Immune-Related Signature for Predicting the Prognosis of Lower-Grade Gliomas

Chen

et al. 2020

Front. Immunol.

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“…Lv et al ., and Jones et al ., also found that IDH1 mutated cases had improved overall survival and progression-free survival in cases of gliomas as compared to IDH1 wild type cases. [ 30 31 ]…”

Section: Discussionmentioning

confidence: 99%

Gliomas - An experience based on molecular markers

Sarma

Khonglah

Mishra

et al. 2021

J Family Med Prim Care

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Background: Gliomas account for 45% of all intracranial tumors. Newer technologies have allowed deeper genetic and epigenetic analysis leading to the discovery of IDH (Isocitrate dehydrogenase) mutations and their association with ATRX (alpha-thalassemia/mental retardation syndrome X-linked) and p53, for better diagnosis and prognosis. In this study, we analysed their expression and correlated with various clinicopathological parameters. A follow up to prognosticate gliomas based on the molecular findings is also attempted. Materials and Method: During last 5 years both retrospective and prospective cases were included in the study. Immunohistochemistry for IDH1, ATRX, and p53 was done and reported based on intensity and percentage of tumor cells expressing the markers. Results: A total of 53 cases of gliomas were included, excluding primary glioblastomas and ependymomas. The patient's age ranged from 10 to 53 years. The male to female ratio was 1.3:1. IDH1 positivity was seen in 88% of diffuse astrocytoma, 80% of anaplastic astrocytoma, 90% of oligodendroglioma, 60% of anaplastic oligodendroglioma, and 54% of glioblastoma. A significant association was seen between positive IDH1 expression and low-grade gliomas ( p = 0.028). A combined analysis of expression of IDH1 and ATRX versus IDH1, ATRX, and p53 with WHO grade showed a statistically significant association. A follow-up of 32 patients was available. Out of 24 IDH1+ (positive) cases, 22 patients had a median survival of 21.5 months (92%). Out of 8 IDH1- (negative) cases, 5 had a median survival of 15.8 months (62%). Conclusion: Gliomas expressing IDH1 mutation show improved survival of patients. Combined analysis of IDH1, ATRX, and p53 has diagnostic and prognostic significance. For routine cases of gliomas, a combination of IDH1 and ATRX are sufficient; however, the use of p53 is recommended for further prognostication and for possible targeted therapy in the future.

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“…LGG and GBM exhibit diverse molecular and clinical features [3]. LGG is more prevalent in younger AGING patients unlike other tumors with a mean age of 41 years [4]. LGG accounts for approximately 15% of all brain and CNS tumors, with an incidence of approximately 1 in 100,000 [5].…”

Section: Introductionmentioning

confidence: 99%

Identification and validation of a novel eight mutant-derived long non-coding RNAs signature as a prognostic biomarker for genome instability in low-grade glioma

Maimaiti

Wang

Pei

et al. 2021

Aging

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Long non-coding RNAs (lncRNAs) comprise an integral part of the eukaryotic transcriptome. Alongside proteins, lncRNAs modulate lncRNA-based gene signatures of unstable transcripts, play a crucial role as antisense lncRNAs to control intracellular homeostasis and are implicated in tumorigenesis. However, the role of genomic instability-associated lncRNAs in low-grade gliomas (LGG) has not been fully explored. In this study, lncRNAs expression and somatic mutation profiles in low-grade glioma genome were used to identify eight novel mutant-derived genomic instability-associated lncRNAs including H19, FLG-AS1, AC091932.1, AC064875.1, AL138767.3, AC010273.2, AC131097.4 and ISX-AS1. Patients from the LGG gene mutagenome atlas were grouped into training and validation sets to test the performance of the signature. The genomic instabilityassociated lncRNAs signature (GILncSig) was then validated using multiple external cohorts. A total of 59 novel genomic instability-associated lncRNAs in LGG were used for least absolute shrinkage and selection operator (Lasso), single and multifactor Cox regression analysis using the training set. Furthermore, the independent predictive role of risk features in the training and validation sets were evaluated through survival analysis, receiver operating feature analysis and construction of a nomogram. Patients with IDH1 mutation status were grouped into two different risk groups based on the GILncSig score. The low-risk group showed a relatively higher rate of IDH1 mutations compared with patients in the high-risk group. Furthermore, patients in the lowrisk group had better prognosis compared with patients in the high-risk group. In summary, this study reports a reliable prognostic prediction signature and provides a basis for further investigation of the role of lncRNAs on genomic instability. In addition, lncRNAs in the signature can be used as new targets for treatment of LGG.

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Isocitrate Dehydrogenase Mutations in Low-Grade Gliomas Correlate With Prolonged Overall Survival in Older Patients

Cited by 7 publications

References 43 publications

An Immune-Related Signature for Predicting the Prognosis of Lower-Grade Gliomas

An Immune-Related Signature for Predicting the Prognosis of Lower-Grade Gliomas

Gliomas - An experience based on molecular markers

Identification and validation of a novel eight mutant-derived long non-coding RNAs signature as a prognostic biomarker for genome instability in low-grade glioma

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