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Genome-wide analysis of circulating tumor DNA methylation profiles in cerebrospinal fluid: a clinical trial of oncolytic virus for glioblastoma [mRNA-Seq]

ABSTRACT: Background: Glioblastoma (GBM) is a common malignant tumor of the central nervous system (CNS) with a poor prognosis and short survival period. A novel tumor lysing virus, Ad-TD-nsIL-12, has demonstrated good anti-tumor properties in preclinical studies. However, there is still a gap in the treatment of GBM with Ad-TD-nsIL-12. Methods: We collected cerebrospinal fluid (CSF) and tumor tissues from patients injected with Ad-TD-nsIL-12 at different times and analyzed CSF circulating tumor DNA (ctDNA) methylation profiles and expression profiles. The differential genes were screened by Lasso Cox regression analyses, and Cox regression analyses. The CIBERSORT algorithm was used to assess the abundance of glioma immune cell infiltration in the TCGA dataset. The role of hub genes in diagnosis, prognosis, and immune cell correlation was analyzed using R software, SPSS software, and Graphpad Prism. Results: By observing the trend of methylation levels in different samples, 3631 differential methylation regions (DMRs) were up-regulated and 497 DMRs were down-regulated after Ad-TD-nsIL-12 injection, and these DMRs recovered their methylation levels within 70-82 days. Combined with the TCGA dataset, eight hub genes were screened to construct diagnostic and prognostic models. There was a significant correlation between hub genes and immune cells. Conclusions: This study analyzed the approximate therapeutic concentrations, doses, and cycles of Ad-TD-nsIL-12 for GBM. Revealed that the hub genes in CSF can be used as a biomarker for the diagnosis and prognosis of GBM, as well as boldly speculated the effect of the hub gene on the immune mechanism of Ad-TD-nsIL-12.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205590 | GEO | 2023/12/01

REPOSITORIES: GEO

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Project description:To further our understanding of the role of DNA methylation in development, Methylated DNA Immunoprecipitation (MeDIP) was used in conjunction with a NimbleGen promoter plus CpG island array to identify Tissue and Developmental Stage specific Differentially Methylated DNA Regions (T-DMRs and DS-DMRs) on a genome-wide basis. Four tissues (brain, heart, liver, and testis) from C57BL/6J mice were analyzed at three developmental stages (15 day embryo, E15; new born, NB; 12 week adult, AD). Almost 5,000 adult T-DMRs and 10,000 DS-DMRs were identified. Surprisingly, almost all DS-DMRs were tissue specific (i.e., methylated and ummenthylated in one or more non-overlapping tissues), indicating that the vast majority of unique sequence DNA methylation has tissue specificity. Also, many DS-DMRs were methylated at early development stages (E15 and NB) but unmethylated in adult, indicating “demethylation” has a prominent role in tissue differentiation. The pattern of DNA methylation in adult testis was dramatically different from somatic tissues in many aspects, mostly notably with a very strong bias of methylation in non-CpGi (CpG island) promoter regions (94%). Although the majority of T-DMRs and DS-DMRs tended to be in non-CpGi promoter regions, a relatively large number were also located in CpGi in promoter, intra-genic and inter-genic regions (>15% of all CpGi). Gene Ontology analysis of genes with methylation in non-CpGi promoters indicates enrichment of genes related to membrane proteins and G-protein coupled receptors. Our data also suggest regulatory roles of DNA methylation outside of promoter regions and in alternative promoter selection. Overall, our studies indicate that change in DNA methylation during development is a dynamic, widespread and tissue-specific process involving both DNA methylation and demethylation. Comparison of DNA methylation across 3 developmental stages (15 day embryo, newborn, and adult) for four tissues (brain, heart, liver and testis)

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Genome-wide analysis of circulating tumor DNA methylation profiles in cerebrospinal fluid: a clinical trial of oncolytic virus for glioblastoma [mRNA-Seq]

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