Evolving Insights into the Molecular Neuropathology of Diffuse Gliomas in Adults

Barthel, Floris P.; Johnson, Kevin C.; Wesseling, Pieter; Verhaak, Roel G.W.

doi:10.1016/j.ncl.2018.04.002

Cited by 7 publications

(8 citation statements)

References 110 publications

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“…To assess the temporal dynamics of serum sPD-L1 in glioma patients, we performed monitoring every 3 Serum was obtained from each subject during routine venipuncture. To remove blood cells, the serum tubes were centrifuged at 2,500×g for 10 min at room temperature.…”

Section: Blood Samplingmentioning

confidence: 99%

“…However, molecular information such as the mutational status of isocitrate dehydrogenase (IDH) genes and the combined deletion of chromosome arms 1p and 19q (1p/19q codeletion) is integral to the 2016 World Health Organization (WHO) criteria for gliomas (2). Thus, these updates have shifted treatment approaches from histological type-based therapy to genotype-based therapy (3). Despite some advances in neurosurgical resection and treatment regimens, the prognosis of patients with high-grade gliomas remains dismal (4).…”

Section: Introductionmentioning

confidence: 99%

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The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

et al. 2020

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Background: Soluble PD-L1 (sPD-L1) in the circulation has been documented to activate global immunosuppression and is considered a predictor of negative clinical outcomes in several malignances. However, the clinical significance of sPD-L1 in the peripheral blood and cerebrospinal fluid (CSF) of patients with glioma remains unclear. Objective: The aim of this study was to detect the correlations of sPD-L1 with clinical features in brain tumors and assess the diagnostic value of this protein in gliomas. Methods: Serum samples were obtained from 73 patients with glioma, 20 patients with meningioma, and 49 healthy controls (HCs) in this study. In total, 31 CSF samples were collected from the matched glioma patients, and seven samples were collected from the matched meningioma patients. The expression of serum sPD-L1 in the glioma cohort was followed for 20 days after surgery to examine the kinetics in the circulation. Inflammatory markers were evaluated based on preoperative blood parameters. The sPD-L1 levels in the serum and CSF were determined by enzyme-linked immunosorbent assay (ELISA). The logistic regression model was used to assess the independent associations of sPD-L1 with gliomas, including high-grade gliomas. Results: Serum and CSF levels of sPD-L1 were significantly elevated in patients with gliomas compared to those with meningiomas and HCs. Additionally, increased levels of sPD-L1 were observed in relatively advanced tumors. sPD-L1 overexpression in the CSF appears to be more representative of aggressive tumor features than overexpression in the serum. For glioma diagnosis, both serum and CSF sPD-L1 showed significant value in the diagnosis and stratification of glioma, and the best diagnostic performance was obtained with serum sPD-L1 rather than blood-based inflammatory markers. In addition, a descending trend in the level of serum sPD-L1 was observed in postoperative patients. Conclusion: In gliomas, elevated circulating and CSF sPD-L1 levels are associated with aggressive biological activities. The results of the current study suggest that sPD-L1 is a promising biomarker for gliomas that can be used in clinical practice.

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Section: Blood Samplingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

et al. 2020

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“…G-CIMP-positive status appears in most WHO grade II and III gliomas and secondary glioblastomas and is correlated with improved patient survival [15]. Other studies used EGFR, NF1, and PDGFRA/IDH1 to classify GBM into pro-neural, neural, classical, and mesenchymal subtypes [16, 17]. Although emerging evidence supports mRNAs as potential biomarkers of glioblastomas, gene expression studies analyzed in isolation usually have inconsistent or discrepant results.…”

Section: Introductionmentioning

confidence: 99%

Integrated analysis of 34 microarray datasets reveals CBX3 as a diagnostic and prognostic biomarker in glioblastoma

et al. 2019

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Background Glioblastomas have a high degree of malignancy, high recurrence rate, high mortality rate, and low cure rate. Searching for new markers of glioblastomas is of great significance for improving the diagnosis, prognosis and treatment of glioma. Methods Using the GEO public database, we combined 34 glioma microarray datasets containing 1893 glioma samples and conducted genetic data mining through statistical analysis, bioclustering, and pathway analysis. The results were validated in TCGA, CGGA, and internal cohorts. We further selected a gene for subsequent experiments and conducted cell proliferation and cell cycle analyses to verify the biological function of this gene. Results Eight glioblastoma-specific differentially expressed genes were screened using GEO. In the TCGA and CGGA cohorts, patients with high CBX3 , BARD1 , EGFR , or IFRD1 expression had significantly shorter survival but patients with high GUCY1A3 or MOBP expression had significantly longer survival than patients with lower expression of these genes. After reviewing the literature, we selected the CBX3 gene for further experiments. We confirmed that CBX3 was overexpressed in glioblastoma by immunohistochemical analysis of tissue microarrays and qPCR analysis of surgical specimens. The functional assay results showed that silencing CBX3 arrests the cell cycle in the G2/M phase, thereby weakening the cell proliferation ability. Conclusions We used a multidisciplinary approach to analyze glioblastoma samples in 34 microarray datasets, revealing novel diagnostic and prognostic biomarkers in patients with glioblastoma and providing a new direction for screening tumor markers. Electronic supplementary material The online version of this article (10.1186/s12967-019-1930-3) contains supplementary material, which is available to authorized users.

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“…A major focus of GBM research over the past decade has been determining and understanding the molecular architecture of GBM predominantly from a genomic, epigenomic and transcriptomic standpoint. Through the efforts of the Cancer Genome Atlas (TCGA) [74] and other consortia, between two to four GBM subtypes have been classified based on transcriptomic profiling: proneural (PN) and mesenchymal (MES) have been most reliably established, with classical (CL) and neural subtypes also described [43, 62, 75]. The PN subtype arises in the frontal cortex of younger patients, accompanied by platelet-derived growth factor receptor-A (PDGFRA) amplification [43, 76], isocitrate dehydrogenase (IDH) 1/2 mutation [42, 43, 77, 78], and tumor protein p53 (TP53) mutations [43, 79, 80].…”

Section: Main Textmentioning

confidence: 99%

“…While the utilization of such tumor classification based on transcriptomic subtypes is not yet widespread in the clinic, it is hoped that through identification and understanding of critical drivers of each GBM subtype, this will lead to more personalized therapeutic approaches for patients and improved survival rates [42, 43, 62, 74, 79]. A significant caveat of this approach with regards to GBM tumors, however is that potential biological targets which are identified based on the biology of the first GBM tumor may not be present in the recurrent tumor [62, 75, 91–93]. Indeed, recent research has put forward the notion that multiple longitudinal specimens sampled from spatially-distinct regions of the tumor are necessary to characterize continuously evolving and high heterogeneous GBMs [94–97].…”

Section: Main Textmentioning

confidence: 99%

System-based approaches as prognostic tools for glioblastoma

et al. 2019

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BackgroundThe evasion of apoptosis is a hallmark of cancer. Understanding this process holistically and overcoming apoptosis resistance is a goal of many research teams in order to develop better treatment options for cancer patients. Efforts are also ongoing to personalize the treatment of patients. Strategies to confirm the therapeutic efficacy of current treatments or indeed to identify potential novel additional options would be extremely beneficial to both clinicians and patients. In the past few years, system medicine approaches have been developed that model the biochemical pathways of apoptosis. These systems tools incorporate and analyse the complex biological networks involved. For their successful integration into clinical practice, it is mandatory to integrate systems approaches with routine clinical and histopathological practice to deliver personalized care for patients.ResultsWe review here the development of system medicine approaches that model apoptosis for the treatment of cancer with a specific emphasis on the aggressive brain cancer, glioblastoma.ConclusionsWe discuss the current understanding in the field and present new approaches that highlight the potential of system medicine approaches to influence how glioblastoma is diagnosed and treated in the future.

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Evolving Insights into the Molecular Neuropathology of Diffuse Gliomas in Adults

Cited by 7 publications

References 110 publications

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

The Clinical Significance of Soluble Programmed Cell Death-Ligand 1 (sPD-L1) in Patients With Gliomas

Integrated analysis of 34 microarray datasets reveals CBX3 as a diagnostic and prognostic biomarker in glioblastoma

System-based approaches as prognostic tools for glioblastoma

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