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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE205591 | GEO | 2023/12/01

REPOSITORIES: GEO

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

Project description: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.

2023-12-01 | GSE205519 | GEO

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

2023-12-01 | GSE205590 | GEO

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

Project description:Genome-wide analysis of circulating tumor DNA methylation profiles in cerebrospinal fluid: a clinical trial of oncolytic virus for glioblastoma

| PRJNA846678 | ENA

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

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

| PRJNA846682 | ENA

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

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

| PRJNA846198 | ENA

Genome-wide methylation analysis of cerebrospinal fluid circulating tumor DNA: a new biomarker for recurrent glioblastoma

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-05-01 | GSE205514 | GEO

Genome-wide methylation analysis of cerebrospinal fluid circulating tumor DNA: a new biomarker for recurrent glioblastoma [MeDIP-Seq]

Project description:Background: Glioblastoma (GBM) is a common malignancy of the central nervous system (CNS) that is prone to recurrent and has a short survival period. Clinical biomarkers for the diagnosis and prognosis of recurrent GBM are lacking.Methods: We collected 4 cerebrospinal fluid (CSF) samples and 1 normal CSF sample from recurrent GBM, as well as paired tissue samples. Genome-wide methylation profiles of CSF circulating tumor DNA (ctDNA) and tissue mRNA transcription profiles were analyzed, and genes were screened by univariate Cox analysis, Lasso regression analysis, and multivariate Cox analysis by the Chinese Glioma Genome Atlas (CGGA) database. Data analysis and visualization were performed using R software, SPSS software, and Graphpad Prism.Results: By taking the intersection of differentially methylated regions (DMRs) and differentially expressed genes (DEGs), 892 genes were selected for Lasso regression analysis and multivariate Cox analysis, and 12 hub genes were finally screened to construct diagnostic and prognostic models. The diagnostic (AUC=0.982) and prognostic (5-years AUC=0.931) models based on the 12 hub genes had high accuracy.Conclusions: This study reveals that 12 hub genes in CSF ctDNA can diagnose and prognosticate recurrent GBM and provide new biomarkers for clinical research into the mechanisms of GBM recurrent.

2023-05-01 | GSE205513 | GEO

Genome-wide methylation analysis of cerebrospinal fluid circulating tumor DNA: a new biomarker for recurrent glioblastoma [mRNA-Seq]

2023-05-01 | GSE205512 | GEO

Exploring genetic alterations in circulating tumor DNA from cerebrospinal fluid of pediatric medulloblastoma.

Project description:Medulloblastoma (MB) is the most common type of brain malignancy in children. Molecular profiling has become an important component to select patients for therapeutic approaches, allowing for personalized therapy. In this study, we successfully identified detectable levels of tumor-derived cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) samples of patients with MB. Furthermore, cfDNA from CSF can interrogate for tumor-associated molecular clues. MB-associated alterations from CSF, tumor, and post-chemotherapy plasma were compared by deep sequencing on next-generation sequencing platform. Shared alterations exist between CSF and matched tumor tissues. More alternations were detected in circulating tumor DNA from CSF than those in genomic DNA from primary tumor. It was feasible to detect MB-associated mutations in plasma of patients treated with chemotherapy. Collectively, CSF supernatant can be used to monitor genomic alterations, as a superior technique as long as tumor-derived cfDNA can be isolated from CSF successfully.

| S-EPMC7952732 | biostudies-literature

Quantitative assessment of circulating tumor cells in cerebrospinal fluid as a clinical tool to predict survival in leptomeningeal metastases.

Project description:PurposeCirculating tumor cells in cerebrospinal fluid are a quantitative diagnostic tool for leptomeningeal metastases from solid tumors, but their prognostic significance is unclear. Our objective was to evaluate CSF-CTC quantification in predicting outcomes in LM.MethodsThis is a single institution retrospective study of patients with solid tumors who underwent CSF-CTC quantification using the CellSearch® platform between 04/2016 and 06/2019. Information on neuroaxis imaging, CSF results, and survival was collected. LM was diagnosed by MRI and/or CSF cytology. Survival analyses were performed using multivariable Cox proportional hazards modeling, and CSF-CTC splits associated with survival were identified through recursive partitioning analysis.ResultsOut of 290 patients with CNS metastases, we identified a cohort of 101 patients with newly diagnosed LM. In this group, CSF-CTC count (median 200 CTCs/3 ml) predicted survival continuously (HR = 1.005, 95% CI: 1.002-1.009, p = 0.0027), and the risk of mortality doubled (HR = 2.84, 95% CI: 1.45-5.56, p = 0.0023) at the optimal cutoff of ≥ 61 CSF-CTCs/3 ml. Neuroimaging findings of LM (assessed by 3 independent neuroradiologists) were associated with a higher CSF-CTC count (median CSF-CTCs range 1.5-4 for patients without radiographic LM vs 200 for patients with radiographic LM, p < 0.001), but did not predict survival.ConclusionOur data shows that CSF-CTCs quantification predicts survival in newly diagnosed LM, and outperforms neuroimaging. CSF-CTC analysis can be used as a prognostic tool in patients with LM and provides quantitative assessment of disease burden in the CNS compartment.

| S-EPMC9119011 | biostudies-literature

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