Observational studyClinical cancer research : an official journal of the American Association for Cancer Research2024
A 5-Hydroxymethylcytosine-Based Noninvasive Model for Early Detection of Colorectal Carcinomas and Advanced Adenomas: The METHOD-2 Study.
Observational study in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03676075 (A Multi-center, Prospective Trial of the Detection of 5-hydroxymethylcytosine), which is not on this map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Multi-center, Prospective Trial of the Detection of 5-hydroxymethylcytosine (5-hmC) in Plasma Cell-free DNA for Establishing a Model for the Early Diagnosis of Colorectal Cancer
Who cites it
7 citing papers in PubMed.
- cfDNA-derived gene signatures as surrogate for microvascular invasion in HCC.JHEP reports : innovation in hepatology · 2026Article
- A 5-hydroxymethylcytosine-based noninvasive model for acute myocardial infarction in type 2 diabetes: implications in cardiovascular outcomes from a 5-year median follow-up study.Cardiovascular diabetology · 2026Article
- Liquid Biopsy in Early Screening of Cancers: Emerging Technologies and New Prospects.Biomedicines · 2026Review
- Cross-Cancer Detectability of ctDNA Biomarkers in Asian Populations: Implications for Pan-Cancer Detection.Cancer management and research · 2026Review
- Brain-derived 5-hydroxymethylcytosine epigenetic scores are related to Alzheimer's disease pathology and cognitive decline.Acta neuropathologica · 2025Article
- 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation.Biomarker research · 2025Review
- Review
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Authors and funding
21 authors.
Funding
Abstract
purposeDetection of colorectal carcinomas at a time when there are more treatment options is associated with better outcomes. This prospective case-control study assessed the 5-hydroxymethylcytosine (5hmC) biomarkers in circulating cell-free DNA (cfDNA) for early detection of colorectal carcinoma and advanced adenomas (AA). EXPERIMENTAL
designPlasma cfDNA samples from 2,576 study participants from the multicenter METHOD-2 study (NCT03676075) were collected, comprising patients with newly diagnosed colorectal carcinoma (n = 1,074), AA (n = 356), other solid tumors (n = 80), and non-colorectal carcinoma/AA controls (n = 1,066), followed by genome-wide 5hmC profiling using the 5hmC-Seal technique and the next-generation sequencing. A weighted diagnostic model for colorectal carcinoma (stage I-III) and AA was developed using the elastic net regularization in a discovery set and validated in independent samples.
resultsDistribution of 5hmC in cfDNA reflected gene regulatory relevance and tissue of origin. Besides being confirmed in internal validation, a 96-gene model achieved an area under the curve (AUC) of 90.7% for distinguishing stage I-III colorectal carcinoma from controls in 321 samples from multiple centers for external validation, regardless of primary location or mutation status. This model also showed cancer-type specificity as well as high capacity for distinguishing AA from controls with an AUC of 78.6%. Functionally, differential 5hmC features associated with colorectal carcinoma and AA demonstrated relevance to colorectal carcinoma biology, including pathways such as calcium and MAPK signaling.
conclusionsGenome-wide mapping of 5hmC in cfDNA shows promise as a highly sensitive and specific noninvasive blood test to be integrated into screening programs for improving early detection of colorectal carcinoma and high-risk AA.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.