Construction of Novel Methylation-Driven Gene Model and Investigation of PARVB Function in Glioblastoma

Yu, Wanli; Wu, Pengfei; Wang, Fang; Li, Miao; Han, Bo; Jiang, Zhiqun

doi:10.3389/fonc.2021.705547

Cited by 6 publications

(13 citation statements)

References 50 publications

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“…Methylation of UPP1 was confirmed as a prognostic factor for GBM multiforme in two bioinformatics analyses (Weng and Salazar, 2021;Yu et al, 2021). UPP1 is a potential biomarker of thyroid cancer, and the possible mechanism of regulating epithelialmesenchymal transition (EMT) plays the role of oncogene (Guan et al, 2019).…”

Section: Figurementioning

confidence: 89%

Multiomics integration reveals the effect of Orexin A on glioblastoma

Yang

Huan²,

Yue³

et al. 2023

Front. Pharmacol.

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Objectives: This study involved a multi-omics analysis of glioblastoma (GBM) samples to elaborate the potential mechanism of drug treatment.Methods: The GBM cells treated with or without orexin A were acquired from sequencing analysis. Differentially expressed genes/proteins/metabolites (DEGs/ DEPs/ DEMs) were screened. Next, combination analyses were conducted to investigate the common pathways and correlations between the two groups. Lastly, transcriptome-proteome-metabolome association analysis was carried out to determine the common pathways, and the genes in these pathways were analyzed through Kaplan-Meier (K-M) survival analysis in public databases. Cell and animal experiments were performed to investigate the anti-glioma activity of orexin A.Results: A total of 1,527 DEGs, 52 DEPs, and 153 DEMs were found. Moreover, the combination analyses revealed that 6, 4, and 1 common pathways were present in the transcriptome-proteome, proteome-metabolome, and transcriptome-metabolome, respectively. Certain correlations were observed between the two data sets. Finally, 11 common pathways were discovered in association analysis, and 138 common genes were screened out in these common pathways. Six genes showed significant differences in terms of survival in both TCGA and CGGA. In addition, orexin A inhibited the proliferation, migration, and invasion of glioma in vitro and in vivo.Conclusion: Eleven common KEGG pathways with six common genes were found among different omics participations, revealing the underlying mechanisms in different omics and providing theoretical basis and reference for multi-omics research on drug treatment.

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Section: Figurementioning

confidence: 89%

Multiomics integration reveals the effect of Orexin A on glioblastoma

Yang

Huan²,

Yue³

et al. 2023

Front. Pharmacol.

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“…Furthermore, studies have reported that GBM patients with MGMT methylation are more sensitive to chemo‐radiotherapy and show a better survival advantage 24 . Recent studies have demonstrated the impact of DNA methylation‐driven alterations on the occurrence and progression of GBM 15,25,26 . The integrated analysis of DNA methylation and gene expression profiles can better analyze the regulatory function of methylation and molecular mechanisms of tumors 14,27 .…”

Section: Discussionmentioning

confidence: 99%

“…However, previous studies mainly focused on single omics and often neglected the complexity of the molecular‐based phenomena landscape 12,13 . To better indicate the transcriptional regulation function of DNA methylation and elucidate the pathogenesis and molecular mechanisms of GBM, recent studies integrated the profiles of DNA methylation and mRNA expression to recognize driven methylated specific genes that are capable of regulating gene expression in cancer, including GBM methylation‐driven genes 14,15 . However, genes for both early diagnosis and prognosis based on DNA methylation‐driven patterns have not been explored for GBM.…”

Section: Introductionmentioning

confidence: 99%

“…12,13 To better indicate the transcriptional regulation function of DNA methylation and elucidate the pathogenesis and molecular mechanisms of GBM, recent studies integrated the profiles of DNA methylation and mRNA expression to recognize driven methylated specific genes that are capable of regulating gene expression in cancer, including GBM methylationdriven genes. 14,15 However, genes for both early diagnosis and prognosis based on DNA methylation-driven patterns have not been explored for GBM. Therefore, it is urgently needed to integrate DNA methylation and mRNA expression data to determine GBM-related driven genes for early diagnosis and prognostic evaluation.…”

Section: Introductionmentioning

confidence: 99%

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Identification and validation of DNA methylation‐driven gene PCDHB4 as a novel tumor suppressor for glioblastoma diagnosis and prognosis

Huang

Xie

Chen

et al. 2023

Molecular Carcinogenesis

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Aberrant DNA methylation is a critical regulator of gene expression in the development and progression of glioblastoma (GBM). However, the impact of methylation‐driven gene PCDHB4 changes on GBM occurrence and progression remains unclear. Therefore, this study aimed to identify the PCDHB4 gene for early diagnosis and prognostic evaluation and clarify its functional role in GBM. Methylation‐driven gene PCDHB4 was selected for GBM using the multi‐omics integration method based on publicly available data sets. The diagnostic capabilities of PCDHB4 methylation and 5‐hydroxymethylcytosines were validated in tissue and blood cell‐free DNA (cfDNA) samples, respectively. Combined survival analysis of PCDHB4 methylation and immune infiltration cells evaluated the prognostic predictive performance of GBM patients. We identified that the PCDHB4 gene achieved high discriminative capabilities for GBM and normal tissues with an area under the curve value of 0.941. PCDHB4 hypermethylation was observed in cfDNA blood samples from GBM patients. Compared with GBM patients with PCDHB4 hypermethylation level, patients with PCDHB4 hypomethylation level had significantly poorer overall survival (p = 0.035). In addition, GBM patients with PCDHB4 hypermethylation and high infiltration of CD4+ T cell activation level had a favorable survival (p = 0.026). Moreover, we demonstrated that mRNA expression of PCDHB4 was downregulated in GBM tissues and upregulated in GBM cell lines with PCDHB4 demethylation, and PCDHB4 overexpression inhibited GBM cell proliferation and migration. In summary, we discovered a novel methylation‐driven gene PCDHB4 for the diagnosis and prognosis of GBM and demonstrated that PCDHB4 is a tumor suppressor in vitro experiments.

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“…Methylation signature has been reported to be associated with survival in glioma, for example, a two-CpG site DNA methylation signature was constructed to predict the prognosis of lower-grade glioma with high accuracy ( Guo W. et al, 2022 ). Additionally, a DNA methylation-driven genes signature was established for risk stratification in GBM ( Yu et al, 2021 ). m6A RNA methylation was reported to regulate the tumorigenesis of glioma.…”

Section: Discussionmentioning

confidence: 99%

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

Wang

Zhang

Jiang

et al. 2022

Front. Cell Dev. Biol.

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Glioma is the most common type of central nervous system tumor with increasing incidence. 7-methylguanosine (m7G) is one of the diverse RNA modifications that is known to regulate RNA metabolism and its dysregulation was associated with various cancers. However, the expression pattern of m7G regulators and their roles in regulating tumor immune microenvironments (TIMEs) as well as alternative splicing events (ASEs) in glioma has not been reported. In this study, we showed that m7G regulators displayed a close correlation with each other and most of them were differentially expressed between normal and glioma tissues. Two m7G signatures were then constructed to predict the overall survival of both GBM and LGG patients with moderate predictive performance. The risk score calculated from the regression coefficient and expression level of signature genes was proved to be an independent prognostic factor for patients with LGG, thus, a nomogram was established on the risk score and other independent clinical parameters to predict the survival probability of LGG patients. We also investigated the correlation of m7G signatures with TIMEs in terms of immune scores, expression levels of HLA and immune checkpoint genes, immune cell composition, and immune-related functions. While exploring the correlation between signature genes and the ASEs in glioma, we found that EIF4E1B was a key regulator and might play dual roles depending on glioma grade. By incorporating spatial transcriptomic data, we found a cluster of cells featured by high expression of PTN exhibited the highest m7G score and may communicate with adjacent cancer cells via SPP1 and PTN signaling pathways. In conclusion, our work brought novel insights into the roles of m7G modification in TIMEs and ASEs in glioma, suggesting that evaluation of m7G in glioma could predict prognosis. Moreover, our data suggested that blocking SPP1 and PTN pathways might be a strategy for combating glioma.

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Construction of Novel Methylation-Driven Gene Model and Investigation of PARVB Function in Glioblastoma

Cited by 6 publications

References 50 publications

Multiomics integration reveals the effect of Orexin A on glioblastoma

Multiomics integration reveals the effect of Orexin A on glioblastoma

Identification and validation of DNA methylation‐driven gene PCDHB4 as a novel tumor suppressor for glioblastoma diagnosis and prognosis

A novel prognostic 7-methylguanosine signature reflects immune microenvironment and alternative splicing in glioma based on multi-omics analysis

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