Understanding Glioblastoma Biomarkers: Knocking a Mountain with a Hammer

Mesrati, Malak Hassn; Behrooz, Amir Barzegar; Abuhamad, Asmaa Y.; Syahir, Amir

doi:10.3390/cells9051236

Cited by 53 publications

(41 citation statements)

References 142 publications

(172 reference statements)

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“…In addition, we cannot rule out inhibitory signals acting on grafted human neural cells. Most striking was the continued expansion of these no longer differentiating transplanted neuroepithelial cells; a behaviour reminiscent of neural cancers such as Glioblastoma that share a similar neural progenitor gene expression profile (Agnihotri et al 2013, Hassn Mesrati et al 2020). In addition to providing novel insight into the regulation of human neural differentiation, this assay may therefore also offer an opportunity to study cancer origins as well as inform cell-based therapeutic approaches to neural injury and disease.…”

Section: Discussionmentioning

confidence: 99%

Human spinal cord differentiation proceeds rapidly in vitro and only initially maintains differentiation pace in a heterologous environment

Dady

Davidson

Halley

et al. 2021

Preprint

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Species-specific differentiation pace in in vitro assays indicates that some aspects of neural differentiation are driven by cell-autonomous processes. Here we describe a novel in vitro human neural rosette assay that recapitulates the temporal sequence of dorsal spinal cord differentiation but proceeds more rapidly than in the human embryonic spinal cord, suggesting that in vitro conditions lack endogenous signalling dynamics. To test the extent to which this in vitro assay represents a cell intrinsic differentiation programme, human iPSC-derived neural rosettes were homo-chronically grafted into the faster differentiating chicken embryonic neural tube. Strikingly, in vitro human differentiation pace was not accelerated, even in single host-integrated cells. Moreover, rosette differentiation eventually stalled in a neural progenitor cell state. These findings demonstrate the requirement for timely extrinsic signalling to accurately recapitulate human neural differentiation tempo, and suggest that while intrinsic properties limit differentiation pace, such signals are also required to maintain differentiation progression

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Section: Discussionmentioning

confidence: 99%

Human spinal cord differentiation proceeds rapidly in vitro and only initially maintains differentiation pace in a heterologous environment

Dady

Davidson

Halley

et al. 2021

Preprint

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“…Based on a recent review evaluating prognostic genes for GBM [ 38 ], we evaluated the possibility of including a second model called ImmuneAngioICIsMesECM as described in Section 2.2 [ 17 , 39 , 48 ]. This procedure created a new set of 6754 CpG probes that were evaluated to classify EDISON positive cases.…”

Section: Resultsmentioning

confidence: 99%

“…We included in the dataset the CpGs related to the genes which were shown to play crucial roles in gliomas. Specifically, we chose: The genes linked to the putative response of immune suppression in the study by Thorston et al [ 18 ]; The genes with the angiomatrix signatures [ 36 ]; The genes associated with the putative response for ICIs in GBMs [ 37 ]; The genes reported as with prognostic value for gliomas by Mesrati et al [ 38 ]; The genes related to the extracellular matrix (ECM) recently linked to the glioma by Zhao et al [ 39 ]. …”

Section: Methodsmentioning

confidence: 99%

A New Epigenetic Model to Stratify Glioma Patients According to Their Immunosuppressive State

Polano

Fabbiani

Adreuzzi

et al. 2021

Cells

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Gliomas are the most common primary neoplasm of the central nervous system. A promising frontier in the definition of glioma prognosis and treatment is represented by epigenetics. Furthermore, in this study, we developed a machine learning classification model based on epigenetic data (CpG probes) to separate patients according to their state of immunosuppression. We considered 573 cases of low-grade glioma (LGG) and glioblastoma (GBM) from The Cancer Genome Atlas (TCGA). First, from gene expression data, we derived a novel binary indicator to flag patients with a favorable immune state. Then, based on previous studies, we selected the genes related to the immune state of tumor microenvironment. After, we improved the selection with a data-driven procedure, based on Boruta. Finally, we tuned, trained, and evaluated both random forest and neural network classifiers on the resulting dataset. We found that a multi-layer perceptron network fed by the 338 probes selected by applying both expert choice and Boruta results in the best performance, achieving an out-of-sample accuracy of 82.8%, a Matthews correlation coefficient of 0.657, and an area under the ROC curve of 0.9. Based on the proposed model, we provided a method to stratify glioma patients according to their epigenomic state.

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“…To better identify GSCs, there has been a significant effort to establish reliable GSC markers. Although still somewhat debated, the most widely accepted and utilized markers of GSCs include CD133, CD44, CD15, CD70, S100A4, ALDH1A3, Nanog, SOX-2, and Nestin [ 32 ] .…”

Section: The Role Of Glioma Stem Cells In Resistancementioning

confidence: 99%

Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review

Singh¹,

Miner²,

Hennis³

et al. 2020

CDR

172

194

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Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and has an exceedingly low median overall survival of only 15 months. Current standard-of-care for GBM consists of gross total surgical resection followed by radiation with concurrent and adjuvant chemotherapy. Temozolomide (TMZ) is the firstchoice chemotherapeutic agent in GBM; however, the development of resistance to TMZ often becomes the limiting factor in effective treatment. While O6-methylguanine-DNA methyltransferase repair activity and uniquely resistant populations of glioma stem cells are the most well-known contributors to TMZ resistance, many other molecular mechanisms have come to light in recent years. Key emerging mechanisms include the involvement of other DNA repair systems, aberrant signaling pathways, autophagy, epigenetic modifications, microRNAs, and extracellular vesicle production. This review aims to provide a comprehensive overview of the clinically relevant molecular mechanisms and their extensive interconnections to better inform efforts to combat TMZ resistance.

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Understanding Glioblastoma Biomarkers: Knocking a Mountain with a Hammer

Cited by 53 publications

References 142 publications

Human spinal cord differentiation proceeds rapidly in vitro and only initially maintains differentiation pace in a heterologous environment

Human spinal cord differentiation proceeds rapidly in vitro and only initially maintains differentiation pace in a heterologous environment

A New Epigenetic Model to Stratify Glioma Patients According to Their Immunosuppressive State

Mechanisms of temozolomide resistance in glioblastoma - a comprehensive review

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