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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 [mRNA-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 | GSE205590 | GEO

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

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

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 [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 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 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 [mRNA-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 | GSE205512 | GEO

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

2023-05-01 | GSE205513 | GEO

Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Project description:Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM)1,2. Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV)3. In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue4. These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 ).

| S-EPMC10620094 | biostudies-literature

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

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