5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation

Abstract Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, and prognosis assessment is essential for improving patient survival rates, enhancing quality of life, and reducing the socioeconomic burden associated with cancer. This goal is crit...

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Main Authors: Danjun Song, Zhou Zhang, Jiaping Zheng, Wei Zhang, Jiabin Cai
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Biomarker Research
Subjects:
Online Access:https://doi.org/10.1186/s40364-025-00751-9
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author Danjun Song
Zhou Zhang
Jiaping Zheng
Wei Zhang
Jiabin Cai
author_facet Danjun Song
Zhou Zhang
Jiaping Zheng
Wei Zhang
Jiabin Cai
author_sort Danjun Song
collection DOAJ
description Abstract Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, and prognosis assessment is essential for improving patient survival rates, enhancing quality of life, and reducing the socioeconomic burden associated with cancer. This goal is critical in precision oncology. Genetic and epigenetic alterations in circulating cell-free DNA (cfDNA) have emerged as transformative tools for advancing early cancer detection, monitoring, and improving patient outcomes. Among these, 5-hydroxymethylcytosine (5hmC) modifications in circulating cfDNA stand out as promising epigenetic markers, offering insights into cancer initiation, progression, metastasis, and prognosis across various cancer types, such as lung cancer, colorectal cancer, and hepatocellular carcinoma. This review comprehensively explores the biology and sequencing methodologies of 5hmC, emphasizing their potential in cancer screening, diagnosis, treatment monitoring, and prognostic assessment. It highlights recent advancements in cfDNA-derived 5hmC signatures’ applications, addressing their strengths and limitations in the context of clinical translation. Furthermore, this review outlines key challenges and future directions for integrating 5hmC modifications in cfDNA into routine clinical practice, facilitating personalized and non-invasive cancer management.
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institution DOAJ
issn 2050-7771
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publishDate 2025-03-01
publisher BMC
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spelling doaj-art-4a1799342feb432cb91a6c4ff805de422025-08-20T03:05:45ZengBMCBiomarker Research2050-77712025-03-0113112010.1186/s40364-025-00751-95-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluationDanjun Song0Zhou Zhang1Jiaping Zheng2Wei Zhang3Jiabin Cai4Department of Liver Surgery, Zhongshan Hospital (Xiamen Branch), Fudan UniversityDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineDepartment of Interventional Therapy, Institute of Hangzhou Medicine, Zhejiang Cancer Hospital, Chinese Academy of SciencesDepartment of Preventive Medicine, Northwestern University Feinberg School of MedicineDepartment of Liver Surgery, Zhongshan Hospital (Xiamen Branch), Fudan UniversityAbstract Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, and prognosis assessment is essential for improving patient survival rates, enhancing quality of life, and reducing the socioeconomic burden associated with cancer. This goal is critical in precision oncology. Genetic and epigenetic alterations in circulating cell-free DNA (cfDNA) have emerged as transformative tools for advancing early cancer detection, monitoring, and improving patient outcomes. Among these, 5-hydroxymethylcytosine (5hmC) modifications in circulating cfDNA stand out as promising epigenetic markers, offering insights into cancer initiation, progression, metastasis, and prognosis across various cancer types, such as lung cancer, colorectal cancer, and hepatocellular carcinoma. This review comprehensively explores the biology and sequencing methodologies of 5hmC, emphasizing their potential in cancer screening, diagnosis, treatment monitoring, and prognostic assessment. It highlights recent advancements in cfDNA-derived 5hmC signatures’ applications, addressing their strengths and limitations in the context of clinical translation. Furthermore, this review outlines key challenges and future directions for integrating 5hmC modifications in cfDNA into routine clinical practice, facilitating personalized and non-invasive cancer management.https://doi.org/10.1186/s40364-025-00751-95-hydroxymethylcytosines (5hmC)Cell-free DNA (cfDNA)Liquid biopsyClinical application
spellingShingle Danjun Song
Zhou Zhang
Jiaping Zheng
Wei Zhang
Jiabin Cai
5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
Biomarker Research
5-hydroxymethylcytosines (5hmC)
Cell-free DNA (cfDNA)
Liquid biopsy
Clinical application
title 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
title_full 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
title_fullStr 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
title_full_unstemmed 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
title_short 5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation
title_sort 5 hydroxymethylcytosine modifications in circulating cell free dna frontiers of cancer detection monitoring and prognostic evaluation
topic 5-hydroxymethylcytosines (5hmC)
Cell-free DNA (cfDNA)
Liquid biopsy
Clinical application
url https://doi.org/10.1186/s40364-025-00751-9
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