DNA Methylation Analysis Identifies Patterns in Progressive Glioma Grades to Predict Patient Survival

Weng, Jing Yin; Salazar, Nicole

doi:10.3390/ijms22031020

Cited by 27 publications

(18 citation statements)

References 58 publications

(66 reference statements)

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“…This suggests that SMOC1 may act as a tumor suppressor. A recent study has analyzed the methylation data of the glioma project from the TCGA database and identified 10 glioma grade-associated cytosine-phosphate guanine sites, which targeted four genes, including SMOC1 (Weng and Salazar, 2021). Another in silico study identified a seven-gene signature, including SMOC1, which was positively correlated with 5-years OS of glioma patients (Zhang G.-H. et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Prognostic Potential of Secreted Modular Calcium-Binding Protein 1 in Low-Grade Glioma

Wang

Xia

Zhao

et al. 2021

Front. Mol. Biosci.

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Background: Secreted modular calcium-binding protein 1 (SMOC1) belongs to a family of matricellular proteins; it was involved in embryo development, endothelial cell proliferation, angiogenesis, integrin–matrix interactions, cell adhesion, and regulation of glucose metabolism. Previous studies showed that the expression of SMOC1 was increased in some tumors. However, the prognostic value and the biological function of SMOC1 in tumor remain unclear.Methods: In this study, we explored the expression profile and prognostic value of SMOC1 in pan-cancers, especially glioma, via multiple databases, including Oncomine, Gene Expression Profiling Interactive 2, PrognoScan, Kaplan–Meier plotter, and the Chinese Glioma Genome Atlas database. Furthermore, LinkedOmics was used to identify the genes coexpressed with SMOC1 and to perform Kyoto Encyclopedia of Genes and Genomes pathways and Gene Ontology analysis in low-grade glioma (LGG). Also, the Cancer Single-Cell State Atlas database was used to evaluate the correlation between SMOC1 expression and functional state activities in glioma cells. In addition, the Tumor Immune Estimation Resource and TISIDB databases were used to evaluate the correlations between SMOC1 expression and tumor-infiltrating immune cells in the tumor microenvironment.Results: Compared with normal brain tissues, the expression of SMOC1 was increased in LGG tissues. The higher expression of SMOC1 was significantly correlated with better survival of LGG patients. Additionally, functional analyses showed that the SMOC1 coexpressed genes were inhibited in processes such as response to type I interferon and interferon-gamma, lymphocyte-mediated immunity, leukocyte migration, adaptive immune response, neutrophil-mediated immunity, T cell activation, and pathways including EMC–receptor interaction, Th17 cell differentiation, and leukocyte trans-endothelial migration in LGG. Moreover, the expression of SMOC1 was correlated with stemness, hypoxia, EMT, and metastasis of glioma cells. Additionally, the expression of SMOC1 expression was negatively correlated with levels of infiltrating B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils and dendritic cells, and gene markers of most immune cells in LGG.Conclusion: Our results suggest that SMOC1 could be a potential biomarker to determine prognosis and might play a specific role in the tumor microenvironment of glioma, thereby influencing the development and progression of glioma. These findings provide some new insights for further investigation.

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Section: Discussionmentioning

confidence: 99%

Prognostic Potential of Secreted Modular Calcium-Binding Protein 1 in Low-Grade Glioma

Wang

Xia

Zhao

et al. 2021

Front. Mol. Biosci.

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“…A study of 60 patient-derived GSC cultures indicated that stratification into distinct clusters based on epigenetic markers can predict patient survival, highlighting the prognostic influence of epigenetic regulation and heterogeneity across tumor samples [ 154 ]. Similarly, identification of methylation markers at CpG sites in GBM samples can predict tumor progression and overall survival [ 155 ].…”

Section: Epigenetic Regulationmentioning

confidence: 99%

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Hersh

Gaitsch

Alomari

et al. 2022

Cancers

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Glioblastoma (GBM) is an aggressive tumor of the central nervous system categorized by the World Health Organization as a Grade 4 astrocytoma. Despite treatment with surgical resection, adjuvant chemotherapy, and radiation therapy, outcomes remain poor, with a median survival of only 14-16 months. Although tumor regression is often observed initially after treatment, long-term recurrence or progression invariably occurs. Tumor growth, invasion, and recurrence is mediated by a unique population of glioblastoma stem cells (GSCs). Their high mutation rate and dysregulated transcriptional landscape augment their resistance to conventional chemotherapy and radiation therapy, explaining the poor outcomes observed in patients. Consequently, GSCs have emerged as targets of interest in new treatment paradigms. Here, we review the unique properties of GSCs, including their interactions with the hypoxic microenvironment that drives their proliferation. We discuss vital signaling pathways in GSCs that mediate stemness, self-renewal, proliferation, and invasion, including the Notch, epidermal growth factor receptor, phosphatidylinositol 3-kinase/Akt, sonic hedgehog, transforming growth factor beta, Wnt, signal transducer and activator of transcription 3, and inhibitors of differentiation pathways. We also review epigenomic changes in GSCs that influence their transcriptional state, including DNA methylation, histone methylation and acetylation, and miRNA expression. The constituent molecular components of the signaling pathways and epigenomic regulators represent potential sites for targeted therapy, and representative examples of inhibitory molecules and pharmaceuticals are discussed. Continued investigation into the molecular pathways of GSCs and candidate therapeutics is needed to discover new effective treatments for GBM and improve survival.

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“…The methylation of specific cytosine bases within gene promoter regions, coupled with the modification of associated histone proteins, comprises the epigenetic control of gene transcription. In glioblastoma, the aberrant hypermethylation of several genes, resulting in transcriptional silencing, is associated with poor patient prognosis [79]. Alternatively, the promoters of transforming genes can become hypomethylated, resulting in aberrantly increased gene expression.…”

Section: A Special Role For Methionine In Dna Methylationmentioning

confidence: 99%

“…The ANXA2 gene product is a positive regulator of the mesenchymal subtype, and loss of DNA methylation in the promoter of the ANXA2 gene can drive mesenchymal transformation [92]. Loss of methylation in promoters of other genes, such as uridine phosphorylase (UPP1), is also associated with decreased survival [79].…”

Section: Potential Consequences Of Methionine Restriction In Glioblas...mentioning

confidence: 99%

Glioblastoma and Methionine Addiction

Sowers

2022

IJMS

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Glioblastoma is a fatal brain tumor with a bleak prognosis. The use of chemotherapy, primarily the alkylating agent temozolomide, coupled with radiation and surgical resection, has provided some benefit. Despite this multipronged approach, average patient survival rarely extends beyond 18 months. Challenges to glioblastoma treatment include the identification of functional pharmacologic targets as well as identifying drugs that can cross the blood-brain barrier. To address these challenges, current research efforts are examining metabolic differences between normal and tumor cells that could be targeted. Among the metabolic differences examined to date, the apparent addiction to exogenous methionine by glioblastoma tumors is a critical factor that is not well understood and may serve as an effective therapeutic target. Others have proposed this property could be exploited by methionine dietary restriction or other approaches to reduce methionine availability. However, methionine links the tumor microenvironment with cell metabolism, epigenetic regulation, and even mitosis. Therefore methionine depletion could result in complex and potentially undesirable responses, such as aneuploidy and the aberrant expression of genes that drive tumor progression. If methionine manipulation is to be a therapeutic strategy for glioblastoma patients, it is essential that we enhance our understanding of the role of methionine in the tumor microenvironment.

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DNA Methylation Analysis Identifies Patterns in Progressive Glioma Grades to Predict Patient Survival

Cited by 27 publications

References 58 publications

Prognostic Potential of Secreted Modular Calcium-Binding Protein 1 in Low-Grade Glioma

Prognostic Potential of Secreted Modular Calcium-Binding Protein 1 in Low-Grade Glioma

Molecular Pathways and Genomic Landscape of Glioblastoma Stem Cells: Opportunities for Targeted Therapy

Glioblastoma and Methionine Addiction

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