Prognostic significance of MGMT methylation and expression of MGMT, P53, EGFR, MDM2 and PTEN in glioblastoma multiforme

Limam, Sarra; Missaoui, Nabiha; Abdessayed, Nihed; Mestiri, S; Selmi, Boulbaba; Mokni, Moncef; Yacoubi, Mohamed Tahar

doi:10.1684/abc.2019.1448

Cited by 18 publications

(22 citation statements)

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“…In LGG patients, eight (5.0%) patients have PTEN mutation and 26 (11.6%) GBM patients have PTEN mutation, which is more than double the rate for LGG, so we conducted that GBM are more incline to PTEN mutation ( P = 0.010). By studying the previous literature, we found that the abovementioned data are consistent with the previously reported data ( 25 – 28 ). In regard to p53 mutational status and MGMT methylation status, we could not find any significant differences.…”

Section: Discussionsupporting

confidence: 91%

Integrated Analysis of the Clinical and Molecular Characteristics of IDH Wild-Type Gliomas in the Chinese Glioma Genome Atlas

et al. 2021

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PurposeCurrent studies and guidelines suggest that the biobehavior of IDH-wild type (IDH-wt) lower-grade glioma (LGG, WHO II-III) is similar to IDH-wt glioblastoma (GBM). However, differences in their clinical and molecular characteristics have not been reported. This study aimed to analyze the clinical and genetic information of gliomas with IDH-wt.Methods389 patients with IDH-wt were enrolled in the study (LGG=165, GBM=224), and their clinical and genetic information was collected from the Chinese Glioma Genome Atlas (CGGA). We conducted an analysis of this information between the two groups of patients and drew conclusions thereof.ResultsThe median age of the LGG patients was 42 (18–74) years, whereas that of the GBM patients was 51 (18–79) years (P < 0.010). GBM patients were more likely to undergo total resection (P = 0.018) and had fewer epileptic seizure symptoms (P < 0.001). The median overall survival (OS) was 55 months for the LGG patients and only 14.83 months for the GBM patients (P < 0.01). The median progression-free survival (PFS) was 44 months for the LGG patients and only 9.767 months for the GBM patients (P < 0.001). GBM patients were more prone to PETN mutations (P = 0.010). Transcriptome analysis showed that the differentially expressed genes in LGG patients were mainly enriched in metabolic pathways and pathways in cancer and in the function of signal transduction and positive regulation of GTPase activity, whereas in GBM patients, they were mainly enriched in the PI3K-Akt signaling pathway and in the functions of apoptotic process and oxidation-reduction process.ConclusionsOur data indicate that these two groups of patients should be re-evaluated and treated differently, despite both having IDH wild type.

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Section: Discussionsupporting

confidence: 91%

Integrated Analysis of the Clinical and Molecular Characteristics of IDH Wild-Type Gliomas in the Chinese Glioma Genome Atlas

et al. 2021

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“…Ninety (91.8%) LGG patients and only 79 (75.2%) GBM patients had wild-type PETN. By studying the previous literature, we found that the above data are consistent with previously reported data [25][26][27][28]. The chi-square test also showed that the probability of PETN mutational status was signi cantly different between IDH-wt LGG and GBM patients (P<0.001).…”

Section: Molecular Pathological Characteristicssupporting

confidence: 91%

Integrated Analysis of the Clinical and Molecular Characteristics of IDH Wild-Type Gliomas in the Chinese Glioma Genome Atlas

Wang

Liu

Zhi

et al. 2021

Preprint

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Purpose: Current studies and guidelines suggest that the biobehavior of IDH-wild type (IDH-wt) lower-grade glioma (LGG, WHO II-III) is similar to IDH-wt glioblastoma (GBM). However, differences in their clinical and molecular characteristics have not been reported. This study aimed to analyze the clinical and genetic information of gliomas with IDH-wt. Methods: Four hundred patients with IDH-wt were enrolled in the study (LGG = 176, GBM = 224), and their clinical and genetic information was collected from the Chinese Glioma Genome Atlas (CGGA). We conducted an analysis of this information between the two groups of patients and drew conclusions thereof. Results: The median age of the LGG patients was 42 (40–47) years, while that of the GBM patients was 51 (47–53) years (P < 0.05). GBM patients were more likely to undergo total resection (P < 0.05) and had fewer epileptic seizure symptoms (P < 0.01). The median overall survival (OS) was 51.87 months for the LGG patients and only 14.5 months for the GBM patients (P < 0.01). The median progression-free survival (PFS) was 37.6 months for the LGG patients and only 9.3 months for the GBM patients (P < 0.01). LGG patients were more prone to PETN mutations (P < 0.05). Transcriptome analysis showed that the differentially expressed genes in LGG patients were mainly enriched in metabolic pathways and pathways in cancer and in the function of signal transduction and positive regulation of GTPase activity, while in GBM patients, they were mainly enriched in the PI3K-Akt signaling pathway and in the functions of apoptotic process and oxidation-reduction process. Conclusions: Our data indicate that these two groups of patients should be re-evaluated and treated differently, despite both having IDH wild type.

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“…Therefore, identification of the biomarkers used for patient classification and targeted drug selection is critical. PTEN, as a key regulator of PI3K/Akt signaling pathway, is demonstrated as a potential prognostic marker of GBM (Kang et al, 2017; Limam et al, 2019). As one of the three key signaling pathways contributing to GBM initiation and progression, PI3K/Akt pathway is a canonical target for GBM treatment (Koul et al, 2006; Narayan et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma

Liu

Yuan

et al. 2019

Front. Pharmacol.

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Dysregulation of retinoblastoma (Rb) signaling pathway have been established as a requirement for glioblastoma (GBM) initiation and progression, which suggests that blockade of CDK4/6-Rb signaling axis for GBM treatment. Palbociclib, a selective inhibitor of the cyclin-dependent kinases CDK4/6, has been applied for breast cancer treatment. However, its efficacy against glioblastoma has not been well clarified. Here, effects of CDK4/6 inhibitors on various kinds of GBM cell lines are investigated and the functional mechanisms are identified. Data showed that cells with diverse PTEN status respond to palbociclib differently. Gain-of-function and loss-of-function studies indicated that PTEN enhanced the sensitivity of GBM cells to palbociclib in vitro and in vivo, which was associated with suppressions of Akt and ERK signaling and independent of Rb signaling inhibition. Hence, our findings support that palbociclib selectively

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Prognostic significance of MGMT methylation and expression of MGMT, P53, EGFR, MDM2 and PTEN in glioblastoma multiforme

Cited by 18 publications

References 0 publications

Integrated Analysis of the Clinical and Molecular Characteristics of IDH Wild-Type Gliomas in the Chinese Glioma Genome Atlas

Integrated Analysis of the Clinical and Molecular Characteristics of IDH Wild-Type Gliomas in the Chinese Glioma Genome Atlas

Integrated Analysis of the Clinical and Molecular Characteristics of IDH Wild-Type Gliomas in the Chinese Glioma Genome Atlas

Involvement of Phosphatase and Tensin Homolog in Cyclin-Dependent Kinase 4/6 Inhibitor-Induced Blockade of Glioblastoma

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