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Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection

ABSTRACT: Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection

PROVIDER: PRJNA837976 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19204600_1.fastq.gz	Fastqsanger.gz
	SRR19204600_2.fastq.gz	Fastqsanger.gz
	SRR19204700_1.fastq.gz	Fastqsanger.gz
	SRR19204700_2.fastq.gz	Fastqsanger.gz
	SRR19204800_1.fastq.gz	Fastqsanger.gz

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Cell-free DNA 5-hydroxymethylcytosine as a marker for common cancer detection

Project description:We used a highly sensitive nano-5hmC-Seal method and profiled the genome-wide distribution of 5-hydroxymethylcytosine (5hmC) in plasma cell-free DNA (cfDNA) from 384 patients with bladder, breast, colorectal, kidney, lung, or prostate cancer and 221 controls. We used machine learning and developed plasma cfDNA 5hmC signatures that are highly sensitive for cancer detection and cancer origin determination. We also identified genes and signaling pathways with aberrant DNA hydroxymethylation in six cancers.

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Bisulfite-free, nano-scale analysis of 5-hydroxymethylcytosine at single base resolution

Project description:High-resolution detection of genome-wide 5-hydroxymethylcytosine (5hmC) sites of small-scale samples represents a continuous challenge. Here, we present CATCH-seq, a bisulfite-free, base-resolution method for the genome-wide detection of 5hmC. CATCH-seq is based on selective 5hmC oxidation, labeling and subsequent C-to-T transition during PCR. Applications of CATCH-seq to nano-scale DNA samples reveal previously underappreciated non-CG 5hmCs in the hESC genome and base-resolution hydroxymethylome in human cell-free DNA.

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Multiplex 5mC Marker Barcode Counting (MMBC-seq): A sensitive detection method for cell-free DNA methylation

Project description:The detection of hypermethylation markers on cell-free DNA (cfDNA) in biological fluids is a promising and non-invasive approach for early diagnosis and monitoring of human diseases. However, it is challenging to detect hypermethylation markers in a high-throughput, sensitive, and cost-effective manner. Here we presented a multiplex 5-methylcytosine marker barcode counting (MMBC-seq) technique and reported its clinical application for cfDNA from peripheral plasma samples. We identified an MMBC cancer detection panel and developed a scoring system to differentiate cancer versus healthy controls. In a multiple-cancer case-control study, the panel achieved a sensitivity and specificity of 80.2% and 95.7% respectively (AUC 0.906, 95% CI 0.846-0.948). The results suggest that MMBC-seq has great potential to realize non-invasive, flexible and clinically applicable cancer detection.

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Detection of early stage pancreatic cancer using 5-hydroxymethylcytosine signatures in circulating cell free DNA

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Cell-free DNA 5-hydroxymethylcytosine is highly sensitive for MRD assessment in acute myeloid leukemia

Project description:Measurable residual disease (MRD) is an important biomarker in acute myeloid leukemia (AML). However, MRD cannot be detected in many patients using current methods. We developed a highly sensitive 5-hydroxymethylcytosine (5hmC) signature in cell-free DNA by analyzing 115 AML patients and 86 controls. The 5hmC method detected MRD in 20 of 29 patients with negative MRD by multiparameter flow cytometry and 11 of 14 patients with negative MRD by molecular methods. MRD detection by the 5hmC method was significantly associated with relapse-free survival. This novel method can be used in most AML patients and may significantly impact AML patient management.

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A Model for the Early Diagnosis of Colorectal Cancer by the Detection of 5-hydroxymethylcytosine (5-hmC) in Plasma Cell-free DNA

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Multiplex 5mC Marker Barcode Counting (MMBC-seq): A sensitive detection method for cell-free DNA methylation

Project description:Multiplex 5mC Marker Barcode Counting (MMBC-seq): A sensitive detection method for cell-free DNA methylation

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5-methylcytosine and 5-hydroxymethylcytosine are synergistic biomarkers for early detection of colorectal cancer

Project description:Background Early cancer detection has the potential to significantly improve treatment outcomes and survival rates. This study investigates the roles of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). Methods We analyzed cfDNA from 37 treatment-naive CRC patients and 32 healthy controls using duet evoC 6-base whole genome sequencing (A, C, T, G, 5mC, 5hmC). We then built CRC classifiers using differentially methylated regions identified in stage IV CRC tissue samples. We compared the performance of models using 5mC-only, 5hmC-only, modified cytosine, or 5mC and 5hmC features. Results Here we show that models combining measurements of 5mC and 5hmC significantly enhance diagnostic accuracy (AUC = 0.95) compared to traditional approaches that conflate these markers (modified C, AUC = 0.66). Notably, of all the DMRs considered, almost half show an increase in 5hmC at stage I and a corresponding decrease in 5mC at stage IV, suggesting that 5hmC can effectively track regions undergoing demethylation during tumor development. Conclusions These results support the hypothesis that distinguishing between 5mC and 5hmC improves the sensitivity of liquid biopsy tests for early-stage cancer detection.

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