scholarly journals Identification of a Prognostic Hypoxia-Associated Gene Set in IDH-Mutant Glioma

2018 ◽  
Vol 19 (10) ◽  
pp. 2903 ◽  
Author(s):  
Philip Dao Trong ◽  
Saskia Rösch ◽  
Heimo Mairbäurl ◽  
Stefan Pusch ◽  
Andreas Unterberg ◽  
...  
Keyword(s):  
Culture Conditions ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Survival Score ◽  
Hypoxic Conditions ◽  
Glioma Growth ◽  
Selection Operator ◽  
Related Survival

Glioma growth is often accompanied by a hypoxic microenvironment favorable for the induction and maintenance of the glioma stem cell (GSC) phenotype. Due to the paucity of cell models of Isocitrate Dehydrogenase 1 mutant (IDH1mut) GSCs, biology under hypoxic conditions has not been sufficiently studied as compared to IDH1 wildtype (IDH1wt) GSCs. We therefore grew well-characterized IDH1mut (n = 4) and IDH1wt (n = 4) GSC lines under normoxic (20%) and hypoxic (1.5%) culture conditions and harvested mRNA after 72 h. Transcriptome analyses were performed and hypoxia regulated genes were further analyzed using the expression and clinical data of the lower grade glioma cohort of The Cancer Genome Atlas (LGG TCGA) in a confirmatory approach and to test for possible survival associations. Results show that global expression changes were more pronounced in IDH1wt than in IDH1mut GSCs. However, when focusing on known hypoxia-regulated gene sets, enrichment analyses showed a comparable regulation in both IDH1mut and IDH1wt GSCs. Of 272 significantly up-regulated genes under hypoxic conditions in IDH1mut GSCs a hypoxia-related survival score (HRS-score) of five genes (LYVE1, FAM162A, WNT6, OTP, PLOD1) was identified by the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm which was able to predict survival independent of age, 1p19q co-deletion status and WHO grade (II vs. III) in the LGG TCGA cohort and in the Rembrandt dataset. Altogether, we were able to identify and validate a novel hypoxia-related survival score in IDH1mut GSCs consisting of five hypoxia-regulated genes which was significantly associated with patient survival independent of known prognostic confounders.

scholarly journals Predicting prognosis and IDH mutation status for patients with lower-grade gliomas using whole slide images

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuai Jiang ◽  
George J. Zanazzi ◽  
Saeed Hassanpour
Keyword(s):  
Performance Metrics ◽  
Small Sample Size ◽  
Small Sample ◽  
The Cancer Genome Atlas ◽  
World Health ◽  
Lower Grade ◽  
Who Grade ◽  
Mutation Status ◽  
Idh Mutations ◽  
Whole Slide Images

AbstractWe developed end-to-end deep learning models using whole slide images of adults diagnosed with diffusely infiltrating, World Health Organization (WHO) grade 2 gliomas to predict prognosis and the mutation status of a somatic biomarker, isocitrate dehydrogenase (IDH) 1/2. The models, which utilize ResNet-18 as a backbone, were developed and validated on 296 patients from The Cancer Genome Atlas (TCGA) database. To account for the small sample size, repeated random train/test splits were performed for hyperparameter tuning, and the out-of-sample predictions were pooled for evaluation. Our models achieved a concordance- (C-) index of 0.715 (95% CI: 0.569, 0.830) for predicting prognosis and an area under the curve (AUC) of 0.667 (0.532, 0.784) for predicting IDH mutations. When combined with additional clinical information, the performance metrics increased to 0.784 (95% CI: 0.655, 0.880) and 0.739 (95% CI: 0.613, 0.856), respectively. When evaluated on the WHO grade 3 gliomas from the TCGA dataset, which were not used for training, our models predicted survival with a C-index of 0.654 (95% CI: 0.537, 0.768) and IDH mutations with an AUC of 0.814 (95% CI: 0.721, 0.897). If validated in a prospective study, our method could potentially assist clinicians in managing and treating patients with diffusely infiltrating gliomas.

scholarly journals Association of TP53 Alteration with Tissue Specificity and Patient Outcome of IDH1-Mutant Glioma

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2116
Author(s):  
Balazs Murnyak ◽  
L. Eric Huang
Keyword(s):  
Patient Outcome ◽  
Tissue Specificity ◽  
Human Cancer ◽  
Lower Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Lower Grade Glioma ◽  
Incidence Studies ◽  
Idh1 Mutations ◽  
Tp53 Status

Since the initial discovery of recurrent isocitrate dehydrogenase 1 (IDH1) mutations at Arg132 in glioma, IDH1 hotspot mutations have been identified in cholangiocarcinoma, chondrosarcoma, leukemia, and various other types of cancer of sporadic incidence. Studies in glioma and leukemia have helped promote the theory that IDH1 mutations are an oncogenic event that drives tumorigenesis in general. Through bioinformatic analysis of more than 45,000 human pan-cancer samples from three independent datasets, we show here that IDH1 mutations are rare events in human cancer but are exclusively prevalent in WHO grade II and grade III (lower-grade) glioma. Interestingly, alterations in the tumor-suppressor gene TP53 (tumor protein p53) co-occur significantly with IDH1 mutations and show a tendency of exclusivity to IDH2 mutations. The co-occurrence of IDH1 mutation and TP53 alteration is widespread in glioma, particularly in those harboring IDH1R132H, IDH1R132G, and IDH1R132S, whereas co-occurrence of IDH1R132C and TP53 alteration can be found sporadically in other cancer types. In keeping with the importance of p53 in tumor suppression, TP53 status is an independent predictor of overall survival irrespective of histological and molecular subgroups in lower-grade glioma. Together, these results indicate tissue specificity of IDH1 hotspot mutation and TP53 alteration and the importance of TP53 status as a predictor of patient outcome in lower-grade glioma.

scholarly journals Survival of diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV: a confirmation of the cIMPACT-NOW criteria

2019 ◽  
Vol 22 (4) ◽  
pp. 515-523 ◽  
Author(s):  
C Mircea S Tesileanu ◽  
Linda Dirven ◽  
Maarten M J Wijnenga ◽  
Johan A F Koekkoek ◽  
Arnaud J P E Vincent ◽  
...  
Keyword(s):  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
World Health ◽  
Lower Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Astrocytic Glioma ◽  
Molecular Features

Abstract Background The Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) has recommended that isocitrate dehydrogenase 1 and 2 wildtype (IDH1/2wt) diffuse lower-grade gliomas (LGGs) World Health Organization (WHO) grade II or III that present with (i) a telomerase reverse transcriptase promoter mutation (pTERTmt), and/or (ii) gain of chromosome 7 combined with loss of chromosome 10, and/or (iii) epidermal growth factor receptor (EGFR) amplification should be reclassified as diffuse astrocytic glioma, IDH1/2 wildtype, with molecular features of glioblastoma, WHO grade IV (IDH1/2wt astrocytomas WHO IV). This paper describes the overall survival (OS) of IDH1/2wt astrocytoma WHO IV patients, and more in detail patients with tumors with pTERTmt only. Methods In this retrospective multicenter study, we compared the OS of 71 IDH1/2wt astrocytomas WHO IV patients, with radiological characteristics of LGGs, with the OS of 197 IDH1/2wt glioblastoma patients. Moreover, we compared the OS of 22 pTERTmt only astrocytoma patients with the OS of the IDH1/2wt glioblastoma patients. Results Median OS was similar for IDH1/2wt astrocytoma WHO IV patients (23.8 mo) and IDH1/2wt glioblastoma patients (19.2 mo) (Cox proportional hazards model: hazard ratio [HR] 1.27, 95% CI: 0.85–1.88, P = 0.242). OS was also similar in patients with IDH1/2wt astrocytomas WHO IV, pTERTmt only, and IDH1/2wt glioblastomas (HR 1.15, 95% CI: 0.64–2.10, P = 0.641). Conclusions The presented data confirm the cIMPACT-NOW recommendation and we propose that IDH1/2wt astrocytomas WHO IV in the absence of other qualifying mutations should be classified as IDH1/2wt glioblastomas.

scholarly journals BICD Cargo Adaptor 1 (BICD1) Downregulation Correlates with a Decreased Level of PD-L1 and Predicts a Favorable Prognosis in Patients with IDH1-Mutant Lower-Grade Gliomas

Biology ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 701
Author(s):  
Shang-Pen Huang ◽  
Chien-Hsiu Li ◽  
Wei-Min Chang ◽  
Yuan-Feng Lin
Keyword(s):  
The Cancer Genome Atlas ◽  
World Health ◽  
Egfr Mutations ◽  
Lower Grade ◽  
Karnofsky Performance Score ◽  
Wild Type ◽  
Who Grade ◽  
Favorable Prognosis ◽  
Potential Biomarker ◽  
Genome Atlas

Although several biomarkers have been identified to predict the prognosis of lower-grade (Grade II/III) gliomas (LGGs), we still need to identify new markers to facilitate those well-known markers to obtain more accurate prognosis prediction in LGGs. Bioinformatics data from The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA), and the Cancer Cell Line Encyclopedia (CCLE) datasets were used as the research materials. In total, 34 genes associated with the HIF1A pathway were analyzed using the hierarchical method to search for the most compatible gene. The BICD cargo adaptor 1 (BICD1) gene (BICD1) was shown to be significantly correlated with The hypoxic inducible factor 1A (HIF1A) expression, the World Health Organization (WHO) grade, and IDH1 mutation status. In addition, BICD1 downregulation was significantly correlated with a higher Karnofsky performance score (KPS), IDH1/TP53/ATRX mutations, wild-type EGFR, and younger patient age in the enrolled LGG cohort. Moreover, BICD1 expression was significantly upregulated in wild-type IDH1 LGGs with EGFR mutations. Kaplan–Meier survival analysis revealed that BICD1 downregulation predicts a favorable overall survival (OS) in LGG patients, especially in those with IDH1 mutations. Intriguingly, we found a significant correlation between BICD1 downregulation and a decreased level of CD274, GSK3B, HGF, or STAT3 in LGGs. Our findings suggest that BICD1 downregulation could be a potential biomarker for a favorable prognosis of LGGs.

scholarly journals Predicting Prognosis and IDH Mutation Status for Patients with Lower-Grade Gliomas Using Whole Slide Images

2021 ◽  
Author(s):  
Shuai Jiang ◽  
George J. Zanazzi ◽  
Saeed Hassanpour
Keyword(s):  
Performance Metrics ◽  
Small Sample Size ◽  
Small Sample ◽  
The Cancer Genome Atlas ◽  
World Health ◽  
Lower Grade ◽  
Who Grade ◽  
Mutation Status ◽  
Idh Mutations ◽  
Whole Slide Images

ABSTRACTWe developed end-to-end deep learning models using whole slide images of adults diagnosed with diffusely infiltrating, World Health Organization (WHO) grade 2 gliomas to predict prognosis and the mutation status of a somatic biomarker, isocitrate dehydrogenase (IDH) 1/2. The models, which utilize ResNet-18 as a backbone, were developed and validated on 296 patients from The Cancer Genome Atlas (TCGA) database. To account for the small sample size, repeated random train/test splits were performed for hyperparameter tuning, and the out-of-sample predictions were pooled for evaluation. Our models achieved a concordance- (C-) index of 0.715 (95% CI: 0.569, 0.830) for predicting prognosis and an area under the curve (AUC) of 0.667 (0.532, 0.784) for predicting IDH mutations. When combined with additional clinical information, the performance metrics increased to 0.784 (95% CI: 0.655, 0.880) and 0.739 (95% CI: 0.613, 0.856), respectively. When evaluated on the grade 3 gliomas TCGA dataset, which was not used for training, our models were able to predict survival with a C-index of 0.654 (95% CI: 0.537, 0.768) and IDH mutations with an AUC of 0.814 (95% CI: 0.721, 0.897). If validated in a prospective study, our method could potentially assist clinicians in managing and treating patients with diffusely infiltrating gliomas.

Lymphocyte-activation gene 3 (LAG-3) expression in the inflammatory microenvironment of glioma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2553-2553
Author(s):  
Maximilian Mair ◽  
Barbara Kiesel ◽  
Katharina Feldmann ◽  
Georg Widhalm ◽  
Karin Dieckmann ◽  
...  
Keyword(s):  
Lymphocyte Activation ◽  
Tumor Infiltrating Lymphocytes ◽  
Age At Diagnosis ◽  
Lower Grade ◽  
Diffuse Glioma ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Inflammatory Microenvironment ◽  
Infiltrating Lymphocytes ◽  
Lymphocyte Activation Gene

2553 Background: The blockade of lymphocyte-activation gene 3 (LAG-3), an inhibitory receptor on tumor-infiltrating lymphocytes, is currently under investigation in many extracranial tumor entities. Methods: 54 patients with diffuse glioma were included: 35 patients with glioblastoma (GBM, median age at diagnosis: 61 years) as well as 14 with WHO grade II and 5 with WHO grade III glioma (lower-grade glioma, LGG, median age at diagnosis: 45 years). Isocitrate dehydrogenase 1/2 mutations (IDH-mt) were present in 17/54 patients and 37/54 patients had IDH wildtype (IDH-wt) tumors. LAG-3 expression on tumor-infiltrating lymphocytes (TILs) was analyzed by immunohistochemistry (monoclonal anti-LAG-3 antibody, clone 17B4, LSBio Inc.). Results: LAG-3+ TILs could be observed in 5/54 (9.3%) samples, while CD3+ TILs were present in 32/54 (59.3%) and CD8+ TILs in 24/54 (44.4%) samples. Only IDH-wt glioma presented with LAG-3+ TILs (p = 0.168). Samples with LAG-3+ TILs presented with a numerical trend towards higher presence of CD3+ (5/27 CD3+ vs. 0/22 CD3−, p = 0.072) and CD8+ TILs (4/24 CD8+ vs. 1/30 CD8−, p = 0.159). 4/7 (57.1%) samples presenting with PD-1+ TILs also presented with LAG-3+ TILs (p = 0.001). Furthermore, glioma samples with LAG3+ TILs presented with higher expression of PD-L1 (median: 1% vs. 0%; p = 0.166). There was no difference in overall survival (OS) according to LAG-3+ TIL infiltration (median OS in LAG-3+: 21.7 months vs. LAG-3−: 41.4 months, p > 0.05). Conclusions: LAG-3+ TILs are rarely observed in IDH-wt and absent in IDH-mt glioma. Gliomas with an active inflammatory microenvironment present more frequently with LAG3+ TILs. The diverse composition of the inflammatory microenvironment and particular inflammatory subgroups should be considered in future clinical trials on immune-modulating therapies in glioma.

scholarly journals A Phase Ib Clinical Trial of Metformin and Chloroquine in Patients with IDH1-Mutated Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2474
Author(s):  
Mohammed Khurshed ◽  
Remco J. Molenaar ◽  
Myra E. van Linde ◽  
Ron A. Mathôt ◽  
Eduard A. Struys ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Solid Tumors ◽  
Intrahepatic Cholangiocarcinoma ◽  
Maximum Tolerated Dose ◽  
Primary Objective ◽  
Idh1 Mutation ◽  
Resonance Spectroscopy ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Phase Ib

Background: Mutations in isocitrate dehydrogenase 1 (IDH1) occur in 60% of chondrosarcoma, 80% of WHO grade II-IV glioma and 20% of intrahepatic cholangiocarcinoma. These solid IDH1-mutated tumors produce the oncometabolite D-2-hydroxyglutarate (D-2HG) and are more vulnerable to disruption of their metabolism. Methods: Patients with IDH1-mutated chondrosarcoma, glioma and intrahepatic cholangiocarcinoma received oral combinational treatment with the antidiabetic drug metformin and the antimalarial drug chloroquine. The primary objective was to determine the occurrence of dose-limiting toxicities (DLTs) and the maximum tolerated dose (MTD). Radiological and biochemical tumor responses to metformin and chloroquine were investigated using CT/MRI scans and magnetic resonance spectroscopy (MRS) measurements of D-2HG levels in serum. Results: Seventeen patients received study treatment for a median duration of 43 days (range: 7–74 days). Of twelve evaluable patients, 10 patients discontinued study medication because of progressive disease and two patients due to toxicity. None of the patients experienced a DLT. The MTD was determined to be 1500 mg of metformin two times a day and 200 mg of chloroquine once a day. A serum D/L-2HG ratio of ≥4.5 predicted the presence of an IDH1 mutation with a sensitivity of 90% and a specificity of 100%. By utilization of digital droplet PCR on plasma samples, we were able to detect tumor-specific IDH1 hotspot mutations in circulating tumor DNA (ctDNA) in investigated patients. Conclusion: Treatment of advanced IDH1-mutated solid tumors with metformin and chloroquine was well tolerated but did not induce a clinical response in this phase Ib clinical trial.

scholarly journals RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Haiwei Wang ◽  
Xinrui Wang ◽  
Liangpu Xu ◽  
Ji Zhang ◽  
Hua Cao
Keyword(s):  
Transcription Factor ◽  
Low Frequency ◽  
Tumor Grade ◽  
The Cancer Genome Atlas ◽  
Lower Grade ◽  
Wild Type ◽  
Lower Grade Glioma ◽  
Cancer Genome Atlas ◽  
Worse Prognosis ◽  
Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

scholarly journals NCOG-38. CLINICAL CHARACTERISTICS OF LOW GRADE GLIOMA PATIENTS WITH NON-CANONICAL IDH1 AND IDH2 MUTATIONS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii137-ii137
Author(s):  
Katherine Peters ◽  
Eric Lipp ◽  
Gloria Broadwater ◽  
James Herndon ◽  
Margaret Johnson ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Point Mutations ◽  
Progression Free Survival ◽  
Idh1 Mutation ◽  
Low Grade ◽  
Isocitrate Dehydrogenase 1 ◽  
Who Grade ◽  
Targeted Mutation ◽  
Kaplan Meier ◽  
Idh1 And Idh2 Mutations

Abstract BACKGROUND Low grade gliomas (LGGs) develop in young adults and represent 10-15% of all glial tumors. While LGG patients can have longer survival than higher grade tumors, progression, transformation, and ultimately mortality occurs. Mutations in Isocitrate dehydrogenase 1/2 (IDH1/IDH2) are prevalent in LGG and are responsible for gliomagenesis. The classic IDH1 mutation is located at 132 codon and represented as p.Arg132His, but there are non-canonical IDH1 and IDH2 mutations. We sought to compare clinical characteristics of LGG patients with classic IDH1 p.Arg132His mutation to LGG patients with non-canonical IDH1 and IDH2 mutations. METHODS We queried an IRB-approved registry retrospectively from 12/2004- 9/2019. We included IDH1/IDH2 mutant LGG (WHO grade II) and known IDH1 and IDH2 targeted mutation analysis using standard PCR followed by DNA sequencing to detect point mutations in IDH1/IDH2 genes. We obtained available clinical and histopathological data. We estimated progression-free survival (PFS), time to transformation (TT), and overall survival (OS) using Kaplan-Meier methods. RESULTS We identified 267 LGG patients with median follow-up of 9.1 yrs (95%CI 8.4-9.9 yrs). Classic IDH1 p.Arg132His mutation occurred in 223 (83.9%) patients. IDH2 mutations occurred in 14 (5.2%) patients. Non-canonical IDH1 mutations were in 30 (11.2%) patients and included the following mutations: p.Arg132Cys (13), p.Arg132Gly (10), p.Arg132Ser (4), p.Arg132Leu (1), p.Arg119Gln (1), and p.Arg172Met (1). Initial presentation, OS, and TT did not differ between IDH1/IDH2 groups. PFS differed significantly between groups with improved median PFS in IDH2 mutant LGG (5.4 yrs; 95%CI 3.5-25.2) versus classic IDH1 mutant LGG (4.1 yrs; 95%CI 3.7-4.9 yrs) and non-canonical IDH1 mutant LGG (2.6 yrs; 95%CI 2.1-4.8) (log-rank p=0.019). Notably, non-canonical mutations were more common in astrocytoma (22/30; 73.3%) than other LGG histologies (p=0.018). CONCLUSIONS In this cohort, LGG patients with non-canonical mutations have a shorter time to progression than patients with classic p.Arg132His mutation and IDH2 mutations.

scholarly journals Heme Biosynthesis mRNA Expression Signature: Towards a Novel Prognostic Biomarker in Patients with Diffusely Infiltrating Gliomas

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 662
Author(s):  
Mario Mischkulnig ◽  
Barbara Kiesel ◽  
Daniela Lötsch ◽  
Thomas Roetzer ◽  
Martin Borkovec ◽  
...  
Keyword(s):  
Overall Survival ◽  
Mrna Expression ◽  
Postoperative Management ◽  
Heme Biosynthesis ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Who Grade ◽  
Expression Signature ◽  
Cancer Genome Atlas ◽  
The Impact

Diffusely infiltrating gliomas are characterized by a variable clinical course, and thus novel prognostic biomarkers are needed. The heme biosynthesis cycle constitutes a fundamental metabolic pathway and might play a crucial role in glioma biology. The aim of this study was thus to investigate the role of the heme biosynthesis mRNA expression signature on prognosis in a large glioma patient cohort. Glioma patients with available sequencing data on heme biosynthesis expression were retrieved from The Cancer Genome Atlas (TCGA). In each patient, the heme biosynthesis mRNA expression signature was calculated and categorized into low, medium, and high expression subgroups. Differences in progression-free and overall survival between these subgroups were investigated including a multivariate analysis correcting for WHO grade, tumor subtype, and patient age and sex. In a total of 693 patients, progression-free and overall survival showed a strictly monotonical decrease with increasing mRNA expression signature subgroups. In detail, median overall survival was 134.2 months in the low, 79.9 months in the intermediate, and 16.5 months in the high mRNA expression signature subgroups, respectively. The impact of mRNA expression signature on progression-free and overall survival was independent of the other analyzed prognostic factors. Our data indicate that the heme biosynthesis mRNA expression signature might serve as an additional novel prognostic marker in patients with diffusely infiltrating gliomas to optimize postoperative management.

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