Relevance of a TCGA-derived Glioblastoma Subtype Gene-Classifier among Patient Populations

Teo, Wan Yee; Sekar, Karthik; Seshachalam, Pratap; Shen, Jianhe; Chow, Wing Yuk; Lau, Ching C.; Yang, Hee Kyoung; Park, Junseong; Kang, Seok‐Gu; Li, Xiaonan; Nam, Do Hyun; Hui, Kam M.

doi:10.1038/s41598-019-43173-y

Cited by 56 publications

(60 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The latest 2016 WHO classification of CNS tumours is a huge step forward as it significantly improves classification of gliomas by incorporating molecular data in a glioma diagnostics. However, discussions about previously described proneural and mesenchymal subtypes are still ongoing [13,14,15]. From all these subtypes, especially, mesenchymal subtype is one of the most consistent subtypes described in the literature [14,15,16].…”

Section: Discussionmentioning

confidence: 97%

Molecular classification of diffuse gliomas

Jakovlevs¹,

Vanags²,

Gardovskis³

et al. 2019

pjp

View full text Add to dashboard Cite

In this study we assessed whether gliomas could be subdivided into different molecular subtypes by immunohistochemistry (IHC) reminiscent of those first described by Verhaak et al. in 2010 (classical, proneural, mesenchymal and neural). We also evaluated the prognostic significance of single molecular factors and searched for significant correlations between markers. In this study, we included 146 patients with glioblastomas (GBMs) and 26 with diffuse astrocytomas (DAs). The glioma samples were tested for PDGFRA, IDH1 R132H, CD44, p53, Ki-67, p21 and p27 expression. We found that gliomas could be subdivided into molecular subtypes by IHC. Fifty per cent of GBMs were of the proneural subtype, 18.5% of mesenchymal subtype and 31.5% were not otherwise classified. However, most of the DAs (92.3%) belonged to the proneural subtype. No prognostic role was found for the molecular subtypes, but predictive roles were noted. Both proneural and mesenchymal molecular subtypes showed a benefit from the addition of chemotherapy and radiotherapy; however, the mesenchymal subtype showed a greater response. Interestingly, the mesenchymal subtype did not receive any benefit from the addition of radiotherapy compared with palliative management and surgery alone. Regarding single molecular markers, only IDH1 R132H was found to have a prognostic role for GBMs. There was a trend towards better survival in tumours with lower PDGFRA expression (p = 0.066). In DAs, PDGFRA and Ki-67 expression had prognostic roles. The following statistically significant correlations were found in GBMs: Ki-67/p53, Ki-67/p27 and p53/PDGFRA; in DAs: p53/ PDGFRA, CD44/PDGFRA, and p21/PDGFRA.

show abstract

Section: Discussionmentioning

confidence: 97%

Molecular classification of diffuse gliomas

Jakovlevs¹,

Vanags²,

Gardovskis³

et al. 2019

pjp

View full text Add to dashboard Cite

show abstract

“…The World Health Organization (WHO, Geneva, Switzerland) classifies GBM based on histopathological findings and molecular features (especially IDH mutation status) [ 4 ]. At a gene-expression level, GBM can be classified into four subtypes: mesenchymal, classical, proneural and neural [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Beyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma

Duraj

García-Romero

Carrión-Navarro

et al. 2021

Cells

View full text Add to dashboard Cite

Glioblastoma (GBM) is the most aggressive primary brain tumor, with a median survival at diagnosis of 16–20 months. Metabolism represents a new attractive therapeutic target; however, due to high intratumoral heterogeneity, the application of metabolic drugs in GBM is challenging. We characterized the basal bioenergetic metabolism and antiproliferative potential of metformin (MF), dichloroacetate (DCA), sodium oxamate (SOD) and diazo-5-oxo-L-norleucine (DON) in three distinct glioma stem cells (GSCs) (GBM18, GBM27, GBM38), as well as U87MG. GBM27, a highly oxidative cell line, was the most resistant to all treatments, except DON. GBM18 and GBM38, Warburg-like GSCs, were sensitive to MF and DCA, respectively. Resistance to DON was not correlated with basal metabolic phenotypes. In combinatory experiments, radiomimetic bleomycin exhibited therapeutically relevant synergistic effects with MF, DCA and DON in GBM27 and DON in all other cell lines. MF and DCA shifted the metabolism of treated cells towards glycolysis or oxidation, respectively. DON consistently decreased total ATP production. Our study highlights the need for a better characterization of GBM from a metabolic perspective. Metabolic therapy should focus on both glycolytic and oxidative subpopulations of GSCs.

show abstract

“…Accumulated genomic and transcriptomic data has reached a sufficient level for use in improving diagnosis and stratification of patients [ 28 ]. A huge effort of the TCGA consortium resulted in the development of many new cancer typing systems, e.g., in colorectal cancer, breast cancer, glioblastoma, and EC [ 29 , 30 , 31 , 32 ]. The primary advantage of molecular typing is less dependence on the knowledge and experience of a pathologist.…”

Section: Discussionmentioning

confidence: 99%

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer

et al. 2021

View full text Add to dashboard Cite

Endometrial cancer (EC) is treated according to the stage and prognostic risk factors. Most EC patients are in the early stages and they are treated surgically. However, some of them, including those with high grade (grade 3) are in the intermediate and high intermediate prognostic risk groups and may require adjuvant therapy. The goal of the study was to find differences between grades based on an miRNA gene expression profile. Tumor samples from 24 patients with grade 1 (n = 10), 2 (n = 7), and 3 (n = 7) EC were subjected to miRNA profiling using next generation sequencing. The results obtained were validated using the miRNA profile of 407 EC tumors from the external Cancer Genome Atlas (TCGA) cohort. We obtained sets of differentially expressed (DE) miRNAs with the largest amount between G2 to G1 (50 transcripts) and G3 to G1 (40 transcripts) patients. Validation of our results with external data (TCGA) gave us a reasonable gene overlap of which we selected two miRNAs (miR-375 and miR190b) that distinguish the high grade best from the low grade EC. Unsupervised clustering showed a high degree of heterogeneity within grade 2 samples. MiR-375 as well as 190b might be useful to create grading verification test for high grade EC. One of the possible mechanisms that is responsible for the high grade is modulation by virus of host morphology or physiology.

show abstract

Relevance of a TCGA-derived Glioblastoma Subtype Gene-Classifier among Patient Populations

Cited by 56 publications

References 38 publications

Molecular classification of diffuse gliomas

Molecular classification of diffuse gliomas

Beyond the Warburg Effect: Oxidative and Glycolytic Phenotypes Coexist within the Metabolic Heterogeneity of Glioblastoma

Low Expression of miR-375 and miR-190b Differentiates Grade 3 Patients with Endometrial Cancer

Contact Info

Product

Resources

About