Molecular and Circulating Biomarkers in Patients with Glioblastoma

Senhaji, Nadia; Houssaini, Asmae Squalli; Lamrabet, Salma; Louati, Sara; Bennis, S.

doi:10.3390/ijms23137474

Cited by 24 publications

(20 citation statements)

References 247 publications

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“…Our findings conform to the “astrocyte dedifferentiation theory” corresponding to glioblastoma origin [ 41 – 43 ]. In contrast to uninfected HAs, the distinct transcriptome profile including oncogenes, tumor suppressor genes and cell cycle genes facilitated the characterization of CEGBCs that possess a glioblastoma-like phenotype [ 44 , 45 ]. Stemness acquisition, commonly described in metastasis and poorly differentiated tumors [ 46 – 48 ], is in accordance with previous findings where GB-generated spheroids are composed of glioma stem cells (GSCs).…”

Section: Discussionmentioning

confidence: 99%

EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes

et al. 2023

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Mounting evidence is identifying human cytomegalovirus (HCMV) as a potential oncogenic virus. HCMV has been detected in malignant gliomas. EZH2 and Myc play a potential oncogenic role, correlating with the glioma grade. Herewith, we present the first experimental evidence for HCMV as a reprogramming vector, straight through the dedifferentiation of mature human astrocytes, and generation of CMV-Elicited Glioblastoma Cells (CEGBCs) possessing glioblastoma-like traits. HCMV counterparts the progression of the perceived cellular and molecular mechanisms succeeding the transformation and invasion processes with CEGBCs involved in spheroid formation and invasiveness. Glioblastoma multiforme (GBM) biopsies were characterized by an elevated EZH2 and Myc expression, possessing a strong positive correlation between the aforementioned markers in the presence of HCMV. From GBM tissues, we isolated HCMV clinical strains that transformed HAs toward CEGBCs exhibiting upregulated EZH2 and Myc. Spheroids generated from CEGBCs possessed invasion potential and were sensitive to EZH2 inhibitor, ganciclovir, and temozolomide triple therapy. HCMV clinical strains transform HAs and fit with an HCMV-induced glioblastoma model of oncogenesis, and supports the tumorigenic properties of Myc and EZH2 which might be highly pertinent in the pathophysiology of astrocytic brain tumors and thereby paving the way for new therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes

et al. 2023

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“…These biological processes may be the intrinsic reasons for glioma adaptive survival, and the correlation between UBE2C and malignant phenotypes of glioma cell also reflects this inference ( Figure 5 ). In addition, since the immunosuppression and cell invasion phenotypes of glioma are difficult in clinical diagnosis and treatment [44, 45], the evaluation of the application value of biomarkers should also focus on these two aspects [46–48]. In this study, UBE2C was found to be significantly positively correlated with immune infiltration of Th2 cells in gliomas ( Figure 6A-C ).…”

Section: Discussionmentioning

confidence: 74%

Systematic Identification of UBE2C As a Prognostic Biomarker and Correlated with Immunosuppression and Invasiveness in Glioma

Feng,

Fu,

Yang

et al. 2024

Preprint

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Glioma is one of the common tumors of the central nervous system, which presents difficulties in clinical diagnosis and treatment due to its characteristics of immunosuppression and cell invasion phenotypes. If the condition and prognosis of glioma can be predicted during the process of diagnosis and treatment, it will be more conducive to timely intervention or evaluation of glioma. Therefore, we still need to search for more valuable tumor markers. The differential/risk genes and enrichment analysis based on glioma samples (The Cancer Genome Atlas, TCGA). Target gene UBE2C were obtained by the expression correlation and differential expression analysis for the enrichment results. UBE2C were evaluated by clinical grading, survival prognosis and cell experiments. The correlation of UBE2C with immune invasion, immune checkpoint, network analysis and cell invasiveness of gliomas was analyzed by TCGA-glioma data and STRING, respectively. The results suggests that the high expression and risk of UBE2C in gliomas may be a factor that promotes malignant phenotype of tumor cells. The immune phenotype shows that IL6 and IL10 may be the key nodes affecting the immunosuppressive phenotype of glioma. Further, the tumor cells aggressive genes from the MMP family can be correlated with immunosuppressive phenotypes via UBE2C-IL6/IL10 axis, especially displayed by MMP2/MMP9. The UBE2C may systemic effects the malignant phenotype, immunosuppression and cell invasiveness of tumors systematically, which reflects UBE2C as a potential biomarker of glioma and therapeutic target for this tumor.

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“…In addition, the length of the DNA fragments and their source in glioblastoma are unknown and the measurement of cfDNA in GBM patients for clinical applications remains a multifaceted problem. Currently, circulating cfDNA and ctDNA fractions are analysed in the context of inflammation, as they appear to be promising potential biomarkers for the early diagnosis or prognosis in glioblastoma [22][23][24]. To date, only two meta-analyses have been reported by MacMahon et al [13] and Jarmuzek et al [25].…”

Section: Of 13mentioning

confidence: 99%

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

Jarmuzek,

Wawrzyniak-Gramacka,

Morawin

et al. 2024

IJMS

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Novel blood-circulating molecules, as potential biomarkers for glioblastoma multiforme (GBM) diagnosis and monitoring, are attracting particular attention due to limitations of imaging modalities and invasive tissue biopsy procedures. This study aims to assess the diagnostic and prognostic values of circulating cell-free DNA (cfDNA) in relation to inflammatory status in GBM patients and to determine the concentration and average size of DNA fragments typical of tumour-derived DNA fractions. Preoperative plasma samples from 40 patients (GBM 65.0 ± 11.3 years) and 40 healthy controls (HC 70.4 ± 5.4 years) were compared. The cfDNA concentrations and lengths were measured using the electrophoresis platform, and inflammatory indices (NLR, PLR, LMR, and SII) were calculated from complete blood cell analysis. More fragmented cfDNA and 4-fold higher 50–700 bp cfDNA concentrations were detected in GBM patients than in healthy controls. The average cfDNA size in the GBM group was significantly longer (median 336 bp) than in the HC group (median 271 bp). Optimal threshold values were 1265 pg/μL for 50–700 bp cfDNA (AUC = 0.857) and 290 bp for average cfDNA size (AUC = 0.814). A Kaplan–Meier survival curves analysis also demonstrated a higher mortality risk in the GBM group with a cut-off >303 bp cfDNA. This study is the first to have revealed glioblastoma association with high levels of cfDNA > 1000 pg/μL of 50–700 bp in length, which can be aggravated by immunoinflammatory reactivity.

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Molecular and Circulating Biomarkers in Patients with Glioblastoma

Cited by 24 publications

References 247 publications

EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes

EZH2-Myc driven glioblastoma elicited by cytomegalovirus infection of human astrocytes

Systematic Identification of UBE2C As a Prognostic Biomarker and Correlated with Immunosuppression and Invasiveness in Glioma

Diagnostic and Prognostic Value of Circulating DNA Fragments in Glioblastoma Multiforme Patients

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