Role of Epstein-Barr Virus in Glioblastoma

Zavala-Vega, Sergio; Palma‐Lara, Icela; Soto, Elizabeth Ortega; Trejo-Solís, Cristina; Arellano, Israel Torres-Ramirez de; Ucharima-Corona, Luis Eduardo; Garcia-Chacón, Guadalupe; Ochoa, Sara A.; Xicohtencatl‐Cortes, Juan; Cruz-Córdova, Ariadna; Jiménez‐Hernández, Elva; Vázquez-Meraz, Eugenio; Mejı́a-Aranguré, Juan Manuel; Guzmán-Bucio, Simón; Rembao-Bojórquez, Daniel; Sánchez‐Gómez, Concepción; Salazar–García, Marcela; Arellano‐Galindo, José

doi:10.1615/critrevoncog.2019032655

Cited by 12 publications

(4 citation statements)

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“…Recent studies have reported a link between glioblastoma and perinatal viral exposure (Akhtar et al, 2018;Dickinson et al, 2002;Limam et al, 2019;Strojnik et al, 2017). Further Epstein-Barr virus has been implicated in glioblastoma etiology (Zavala-Vega et al, 2019). Moreover, some studies have also reported that cytomegalovirus (CMV) promotes murine glioblastoma growth via pericyte recruitment and angiogenesis (Krenzlin et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Spatial reference and alternative proteome analysis of glioblastoma reveals molecular signatures and associates survival with specific markers

Duhamel

Drelich

Wisztorski

et al. 2022

Preprint

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Molecular heterogeneity is a key feature of glioblastoma pathology impeding patient’s stratification and leading to high discrepancies between patients mean survivals. We performed a spatial proteomics analysis on a cohort of 96 glioblastoma patients with survival varying from few months to more than 4 years. 46 tumors were analyzed by spatially-resolved high resolution mass spectrometry proteomics. Integrative analysis of protein expression and clinical information allowed us to identify three molecular regions associated with immune, neurogenesis and tumorigenesis signatures. Several of these molecular signatures can be enriched within the same tumor sample leading to high intra-tumoral heterogeneity. Nevertheless, a set of proteins was found statistically significant based on patient’s survival times, 10 of which stem from alternative AltORF or non-coding RNA. From these proteins, 5 were selected as survival markers. Classification of patients based on the expression of these 5 proteins leads to a clear difference in survival. The expression of these 5 proteins was validated by immunofluorescence on an external cohort of 50 glioblastoma patients, with a similar correlation with their survival. Taken together, our work has enabled the characterization of new molecular regions within glioblastoma tissues based on protein expression which can help to guide glioblastoma prognosis and to improve the current glioblastoma classification.

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Section: Discussionmentioning

confidence: 99%

Spatial reference and alternative proteome analysis of glioblastoma reveals molecular signatures and associates survival with specific markers

Duhamel

Drelich

Wisztorski

et al. 2022

Preprint

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“…Recent studies have reported a link between glioblastoma and perinatal viral exposure (68–71). It has recently been shown that Epsein-Barr virus can be implicated in GBM etiology (72). Moreover, some recent works have also reported that Cytomegalovirus (CMV) promotes murine glioblastoma growth via pericytes recruitment and angiogenesis (73).…”

Section: Discussionmentioning

confidence: 99%

Overall patient’s survival of glioblastoma associated to molecular markers: a pan-proteomic prospective study

Drelich

Duhamel

Wisztorski

et al. 2020

Preprint

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SUMMARYMolecular heterogeneities are a key feature of glioblastoma (GBM) pathology impeding patient’s stratification and leading to high discrepancies between patients mean survivals. Here, we established a molecular classification of GBM tumors using a pan-proteomic analysis. Then, we identified, from our proteomic data, 2 clusters of biomarkers associated with good or bad patient survival from 46 IDH wild-type GBMs. Three molecular groups have been identified and associated with systemic biology analyses. Group A tumors exhibit neurogenesis characteristics and tumorigenesis. Group B shows a strong immune cell signature and express poor prognosis markers while group C tumors are characterized by an anti-viral signature and tumor growth proteins. 124 proteins were found statistically different based on patient’s survival times, of which 10 are issued from alternative AltORF or non-coding RNA. After statistical analysis, a panel of markers associated to higher survival (PPP1R12A, RPS14, HSPD1 and LASP1) and another panel associated to lower survival (ALCAM, ANXA11, MAOB, IP_652563 and IGHM) has been validated by immunofluorescence. Taken together, our data will guide GBM prognosis and help to improve the current GBM classification by stratifying the patients and may open new opportunities for therapeutic development.SignificanceGlioblastoma are very heterogeneous tumors with median survivals usually inferior to 20 months. We conducted a pan-proteomics analysis of glioblastoma (GBM) in order to stratify GBM based on the molecular contained. Forty-six GBM cases were classified into three groups where proteins are involved in specific pathways i.e. the first group has a neurogenesis signature and is associated with a better prognosis while the second group of patients has an immune profile with a bad prognosis. The third group is more associated to tumorigenesis. We correlated these results with the TCGA data. Finally, we have identified 28 new prognostic markers of GBM and from these 28, a panel of 4 higher and 5 lower survival markers were validated. With these 9 markers in hand, now pathologist can stratify GBM patients and can guide the therapeutic decision.HighlightsA novel stratification of glioblastoma based on mass spectrometry was established.Three groups with different molecular features and survival were identified.This new classification could improve prognostication and may help therapeutic options.8 prognosis markers for oncologist therapeutic decision have been validated.

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“…EBV RNA/DNA, miRNAs and proteins were also present in the plasma of GBM patients, and their EBV titers were significantly higher than those of controls. Furthermore, EBV-associated LMP1, LMP2, EBER, EBNA, and BART play important roles in the differentiation, proliferation, and apoptosis of tumor cells, suggesting that EBV is involved in the pathogenesis of GBM, although the mechanisms remain elusive ( Zavala-Vega et al, 2019 ; Strojnik et al, 2017 ). Aberrantly expressed miRNAs can be detected in patients with gliomas ( Karimzadeh et al, 2021 ).…”

Section: Ebv and Brain Tumorsmentioning

confidence: 99%

Epstein-Barr Virus and Neurological Diseases

Zhang

Zuo

Jiang

et al. 2022

Front. Mol. Biosci.

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Epstein-Barr virus (EBV), also known as human herpesvirus 4, is a double-stranded DNA virus that is ubiquitous in 90–95% of the population as a gamma herpesvirus. It exists in two main states, latent infection and lytic replication, each encoding viral proteins with different functions. Human B-lymphocytes and epithelial cells are EBV-susceptible host cells. EBV latently infects B cells and nasopharyngeal epithelial cells throughout life in most immunologically active individuals. EBV-infected cells, free viruses, their gene products, and abnormally elevated EBV titers are observed in the cerebrospinal fluid. Studies have shown that EBV can infect neurons directly or indirectly via infected B-lymphocytes, induce neuroinflammation and demyelination, promote the proliferation, degeneration, and necrosis of glial cells, promote proliferative disorders of B- and T-lymphocytes, and contribute to the occurrence and development of nervous system diseases, such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, acute cerebellar ataxia, meningitis, acute disseminated encephalomyelitis, and brain tumors. However, the specific underlying molecular mechanisms are unclear. In this paper, we review the mechanisms underlying the role of EBV in the development of central nervous system diseases, which could bebeneficial in providing new research ideas and potential clinical therapeutic targets for neurological diseases.

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Role of Epstein-Barr Virus in Glioblastoma

Cited by 12 publications

References 0 publications

Spatial reference and alternative proteome analysis of glioblastoma reveals molecular signatures and associates survival with specific markers

Spatial reference and alternative proteome analysis of glioblastoma reveals molecular signatures and associates survival with specific markers

Overall patient’s survival of glioblastoma associated to molecular markers: a pan-proteomic prospective study

Epstein-Barr Virus and Neurological Diseases

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