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Observational study to investigate the correlations between the circulating tumor DNA and clinicopathological features of metastatic lesion

ABSTRACT: Primary outcome(s): Correlations between pathological features and status of ctDNA detection in tissue samples of metastatic organs Correlations between ctDNA detection status and clinical information, including radiological images Significance of exosome analysis in cases in which ctDNA is difficult to detect

DISEASE(S): Colorectal Cancer

PROVIDER: 2661362 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Analysis of ctDNA methylation induced by ionizing to different ograns

Project description:This study aims to compared ctDNA methylation status induced by ionizing to different ograns. SD rats were irradiated with local radaition to brain, lung or skin. Serum was collected and subjiected to ctDNA extraction. ctDNA were then treated by methylation-sensive bisulfite and sequencing.

2021-12-23 | GSE163763 | GEO

Reliable tumor detection using cerebrospinal fluid cell-free DNA methylomes in pediatric medulloblastoma

Project description:Medulloblastoma (MB) is an embryonal tumor of the cerebellum and a highly malignant childhood brain tumor. Cell-free circulating tumor DNA (ctDNA) from the cerebrospinal fluid (CSF) of patients with brain tumors faithfully represent genomic alterations of brain tumors. Distinct epigenetic signatures among subgroups of MB allow us to detect epigenetic alterations in CSF to aid classify and guide therapy of MB tumors. Here, we evaluate DNA methylation and hydroxymethylation of ctDNA derived from small amount of CSF (200 µL) and matched tumor DNA from 3 MB patients. We find highly concordance of DNA methylation and hydroxymethylation between CSF ctDNA and tumor DNA, especially in CpG islands. Importantly, CSF ctDNA can mostly recapitulate the dynamic changes of DNA methylation and hydroxymehtylation in tumor species compared to healthy cerebellums. Those MB tumor signature CpGs’ DNA methylation status are recovered in CSF ctDNA can clearly distinguish MB subgroups by utilizing public large cohort data. We further identified potential diagnostic and prognostic DNA methylation markers in CSF ctDNA. Our results show that CSF ctNDA methylation and hydroxymethylation can be a minimal invasive method to assess epigenetic alterations of MB, which is complementary to current diagnoses of MB tumors.

2020-10-28 | GSE142241 | GEO

Associations of P16INK4a promoter hypermethylation with squamous intra-epithelial lesion, cervical cancer and their clinicopathological features: a meta-analysis.

Project description:To assess the associations of P16INK4a methylation status with low-grade squamous intra-epithelial lesion (LSIL), high-grade squamous intra-epithelial lesion (HSIL), cervical cancer (CC) and their clinicopathological features, a meta-analysis with 29 eligible studies was conducted. Pooled odds ratios (ORs) with their 95% confidence intervals (CIs) were estimated to assess the strength of the associations. Heterogeneity, sensitivity of pooled results and publication bias were also evaluated. Overall, there was an increasing trend of P16INK4a hypermethylation rates among LSIL (21.4%), HSIL (30.9%) and CC (35.0%) specimens. P16INK4a hypermethylation was significantly associated with the increased risk of LSIL, HSIL and CC, with the pooled ORs of 3.26 (95% CI: 1.86-5.71), 5.80 (95% CI: 3.80-8.84) and 12.17 (95% CI: 5.86-25.27), respectively. A significant association was also found between P16INK4a hypermethylation and smoking habit (OR = 3.88, 95% CI: 2.13-7.08). Taken together, meta-analysis results support P16INK4a hypermethylation as an epigenetic marker for the progression of cervical carcinogenesis.

| S-EPMC5352104 | biostudies-literature

Altered Biogenesis and MicroRNA Content of Hippocampal Exosomes Following Experimental Status Epilepticus

Project description:Here, we characterised the effects of experimental status epilepticus on the expression of exosome biosynthesis components and analysed microRNA content in exosome-enriched fractions prepared from the mouse hippocampus. Status epilepticus induced by unilateral intra-amygdala kainic acid resulted in acute subfield-specific, bi-directional changes in transcripts associated with exosome biosynthesis including up-regulation of ESCRT–dependent and –independent pathways. Increased expression of exosome components including Alix were detectable in samples obtained two weeks after status epilepticus and changes occurred in both the ipsilateral and contralateral hippocampus. Small RNAseq analysis of exosome-enriched fractions prepared using two different techniques detected a rich diversity of conserved microRNAs and determined status epilepticus selectively alters microRNA contents, including upregulation of the glia-enriched miR-21a-3p. We also characterized editing sites of the exosome-enriched miRNAs and found six exosome-enriched miRNAs that were Adenosine-to-Inosine (ADAR) edited with the majority of the editing events predicted to occur within miRNA seed regions. However, the prevalence of these editing events was not altered by status epilepticus. These studies demonstrate status epilepticus alters the exosome pathway and its microRNA content, but not editing patterns.

2019-12-12 | GSE136695 | GEO

Isoform-level Transcriptome Analysis of Peripheral Blood Mononuclear Cells from Breast Cancer Patients Identifies a Disease-associated RASGEF1A isoform

Project description:Breast cancer (BC) comprises multiple subtypes with distinct molecular features, which differ in their interplay with host immunity, prognosis, and treatment. The triple-negative and HER2(+) subtypes are generally more immunogenic and associated with better immunotherapy responsiveness than the luminal subtypes. Non-invasive blood analyses can provide valuable insights into systemic immunity during cancer. The aim of this study was to analyze the expression of transcriptional isoforms in peripheral blood mononuclear cells (PBMCs) from BC patients and healthy women to identify potential BC immune biomarkers. RNA-sequencing and isoform-level bioinformatics were performed on PBMCs from 13 triple-negative and 13 luminal A patients. Isoform expression validation by qRT-PCR and clinicopathological correlations were performed in a larger cohort (156 BC patients and 32 healthy women). Transcriptional analyses showed a significant (p<.001) decrease of the ENST00000374459 RASGEF1A isoform in PBMCs of BC compared to healthy subjects, indi-cating disease-related expression changes. The decrease was associated with higher ctDNA and Ki-67 values. The levels of the RASGEF1A transcriptional isoform ENST00000374459 may have the potential to distinguish between BC and healthy subjects. The downregulation of ENST00000374459 in breast cancer is associated with higher proliferation and ctDNA shedding. Specialized bioinformatics analyses such as isoform analyses hold significant promise in the detection of biomarkers, since variant-indiscriminate (standard) RNA sequencing analyses may overlook specific transcriptional changes that may be disease-associated and biologically important.

2024-09-13 | GSE270376 | GEO

Circulating tumor DNA for monitoring classic Hodgkin lymphoma patients: correlation with FDG-PET/CT

Project description:Circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients are still not well-defined. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high PBatial and temporal heterogeneity. Though ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based in total ctDNA quantification, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.

2023-12-18 | GSE244989 | GEO

A prospective study on prediction of recurrence and prognosis for colorectal cancer using circulating tumor DNA (ctDNA)/exomeDNA in plasma and urine

Project description:Primary outcome(s): The correlation of the dose of ctDNA and exosome DNA during treatment and the survival.

| 2661312 | ecrin-mdr-crc

A prospective study on prediction of efficacy of preoperative chemotherapy for patients with liver metastases from colorectal cancer using liquid biopsy

Project description:Primary outcome(s): The correlation of the dose of ctDNA and exosome DNA during treatment and the survival.

| 2661314 | ecrin-mdr-crc

Genome-Wide High-Resolution Mapping of Exosome Substrates Reveals Hidden Features in the Arabidopsis Transcriptome

Project description:The exosome complex plays a central role in RNA metabolism, and each of its core subunits is essential for viability in yeast However, comprehensive studies of exosome substrates and functional analyses of its subunits in multi.CELlular eukaryotes are lacking Here we show that, in sharp contrast to yeast and metazoan exosome complexes, individual subunits of the plant exosome core are functionally specialized Using whole-genome oligonucleotide tiling microarray analyses of csl4 null mutant plants and conditional genetic depletions of RRP4 and RRP41, we uncovered unexpected functional plasticity in the plant exosome core as well as generated a set of high-resolution genome-wide maps of Arabidopsis exosome targets These analyses provide evidence for widespread polyadenylation- and exosome-mediated RNA quality control in plants and reveal novel aspects of stable structural RNA metabolism Finally, numerous novel exosome substrates were discovered, including a select subset of mRNAs, miRNA processing intermediates, and hundreds of noncoding RNAs, the vast majority of which have not been previously described This large collection of RNAs belong to a Òdeeply hiddenÓ layer of the transcriptome that is tightly repressed and can only be visualized upon inhibition of exosome activity These first genome-wide maps of exosome substrates will aid in illuminating new fundamental components and regulatory mechanisms of eukaryotic transcriptomes Keywords: Strand-specific gene expression analysis using whole-genome oligonucleotide tiling microarray analyses of three exosome subunits, using csl4 null mutant plants and conditional genetic depletions of RRP4 and RRP41.

2007-12-28 | GSE9317 | GEO

Gene expression in extra-embryonic tissues flushed out at D18 from heifers, early and late lactating cows

Project description:Evaluate the influence of maternal metabolism on gene expression profiles from extra-embryonic tissues at D18 Keyword: Holstein Heifers and Postpartum dairy cows, metabolism and energy status, elongation and gastrulation, extra-embryonic tissues, transcriptome, correlations between genes & metabolites?

2014-02-04 | GSE46940 | GEO

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