The landscape of the mesenchymal signature in brain tumours

Behnan, Jinan; Finocchiaro, Gaetano; Hanna, Gabi

doi:10.1093/brain/awz044

Cited by 271 publications

(263 citation statements)

References 129 publications

(380 reference statements)

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“…In 2013, Bhat et al found that PN GSCs transformed to the MES state through the NF-κB pathway, with an elevated expression of CD44 and radioresistant phenotypes 37 . Thereafter, several studies were conducted to elucidate the potential mechanisms of how gliomas acquire the MES-signature through activating NF-κB transcriptional programs [38][39][40][41] . Furthermore, therapeutic approaches targeting the NF-κB pathway in GBM have (see figure on previous page) Fig.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-induced lncRNA PDIA3P1 promotes mesenchymal transition via sponging of miR-124-3p in glioma

Wang

Gao

et al. 2020

Cell Death Dis

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Hypoxia is a critical factor in the malignant progression of glioma, especially for the highly-invasive mesenchymal (MES) subtype. But the detailed mechanisms in hypoxia-induced glioma MES transition remain elusive. Pseudogenes, once considered to be non-functional relics of evolution, are emerging as a critical factor in human tumorigenesis and progression. Here, we investigated the clinical significance, biological function, and mechanisms of protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) in hypoxia-induced glioma MES transition. In this study, we found that PDIA3P1 expression was closely related to tumor degree, transcriptome subtype, and prognosis in glioma patients. Enrichment analysis found that high PDIA3P1 expression was associated with epithelial-mesenchymal transition, extracellular matrix (ECM) disassembly, and angiogenesis. In vitro study revealed that overexpression of PDIA3P1 enhanced the migration and invasion capacity of glioma cells, while knockdown of PDIA3P1 induced the opposite effect. Further studies revealed that PDIA3P1 functions as a ceRNA, sponging miR-124-3p to modulate RELA expression and activate the downstream NF-κB pathway, thus promoting the MES transition of glioma cells. In addition, Hypoxia Inducible Factor 1 was confirmed to directly bind to the PDIA3P1 promotor region and activate its transcription. In conclusion, PDIA3P1 is a crucial link between hypoxia and glioma MES transition through the PDIA3P1-miR-124-3p-RELA axis, which may serve as a prognostic indicator and potential therapeutic target for glioma treatment.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-induced lncRNA PDIA3P1 promotes mesenchymal transition via sponging of miR-124-3p in glioma

Wang

Gao

et al. 2020

Cell Death Dis

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“…103,104 CTCs have been found to be significantly associated with the prognosis of patients with brain cancer, with >5 times the CTC count noted among patients with progressive versus stable glioblastoma, and CTCs with a mesenchymal signature, a subtype correlated with tumor resistance to radiotherapy and chemotherapy, have been detected and reported to demonstrate promise for prognosis and treatment guidance. 105 CTCs also have been detected in cases of pituitary adenoma. 106 This type of tumor generally is considered to be benign, but disease recurrence is problematic because many patients are asymptomatic.…”

Section: Ctcs and Cns Cancersmentioning

confidence: 99%

“…CTCs have been detected for human glioblastoma, the most common and a highly aggressive and invasive brain cancer . CTCs have been found to be significantly associated with the prognosis of patients with brain cancer, with >5 times the CTC count noted among patients with progressive versus stable glioblastoma, and CTCs with a mesenchymal signature, a subtype correlated with tumor resistance to radiotherapy and chemotherapy, have been detected and reported to demonstrate promise for prognosis and treatment guidance …”

Section: Introductionmentioning

confidence: 99%

Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

Jin

Chen

Lan³

et al. 2019

Cancer Cytopathology

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The process of metastasis is characterized by the shedding of tumor cells into the bloodstream, where they are transported to other parts of the body to seed new tumors. These cells, known as circulating tumor cells (CTCs), have the potential to reveal much about an individual cancer case, and theoretically can aid in the prediction of outcomes and design of precision treatments. Recent advances in technology now allow for the robust and reproducible characterization of CTCs from a simple blood draw. Both the number of circulating cells and important molecular characteristics correlated with clinical phenotypes such as drug resistance can be obtained and used for real‐time prognostic analysis. Molecular characterization can provide a snapshot of the activity of the main tumor (serving as a “liquid biopsy”) and early warnings concerning changes such as the development of resistance, and aid in predicting the efficacy of different therapeutic approaches for treatment optimization. Herein, the authors review the current clinical use of CTCs as prognostic biomarkers for several different cancers. The quantification of CTCs can lead to more accurate staging and decision making regarding options such as adjuvant chemotherapy.

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“…The role of EMT in non-epithelial tumours like malignant glioma is nonetheless uncertain. However, recent classification of mesenchymal subgroup of GBM strengthen the notion of glial-mesenchymal transition (GMT) similar to EMT-like process in glioma and may contribute to tumour progression, chemo-resistance and tumour relapse regardless of tumour grades (7). Several studies have investigated the expression of EMT markers such as vimentin, TWIST, SNAIL, E-cadherin and N-cadherin in malignant gliomas and demonstrated their apparent role in invasion, drug resistance and tumour recurrence (8)(9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

Beevi¹,

Verma²,

Panigrahi

et al. 2020

Preprint

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Background: Low-grade gliomas are mostly played down as less fatal malignancy despite the fact that most of them eventually progress to high grade thereby leading to death. In vitro glioma cultures have been emerged as a standard model to get insight into phenotypic transformation, drug response and tumor relapse. In this study, attempt was made to establish comprehensive patient-specific short-term cultures comprising of both low-grade and high-grade malignant glioma.Methods: 50 patients with MRI diagnosed malignant glioma were recruited for this study. Fresh surgical tumor tissues were used for the establishment of primary culture. Patients' samples were analyzed for the presence of IDH1/2 mutations, 1p/19q co-deletion, MIB1 and p53. Established primary glioma culture were evaluated for proliferation rate, sensitivity to temozolomide and expression pattern of Glial-Mesenchymal Transition (GMT) markers. Results: Short-term glioma cultures were successfully established in 40 clinical samples. Glioma cultures, irrespective of tumor grades, displayed two distinct pattern of growth kinetics -one with shorter doubling time (high-proliferating) and another group with longer doubling time (lowproliferating). Significant distinctive features were noticed between these two groups in terms of response to temozolomide, expression pattern of GMT markers and their association with clinical/pathological features of malignant glioma. Conclusion: Our findings effectively demonstrated the practicality of development of short-term glioma culture model toward a functional approach for personalized medicine. Our model further revealed the presence of highly proliferative, drug-resistant phenotype among low-grade gliomas. Hence, short-term culture model could be an important prognostic tool to predict patient clinical responses and also provide cue about imminent tumour relapse.

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The landscape of the mesenchymal signature in brain tumours

Cited by 271 publications

References 129 publications

Hypoxia-induced lncRNA PDIA3P1 promotes mesenchymal transition via sponging of miR-124-3p in glioma

Hypoxia-induced lncRNA PDIA3P1 promotes mesenchymal transition via sponging of miR-124-3p in glioma

Current progress in the clinical use of circulating tumor cells as prognostic biomarkers

Patients’ Derived Short-Term Glioma Culture: Identification of Aggressive, Drug-Resistant Phenotype

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