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Review

Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review)

  • Authors:
    • Chenxi Su
    • Jiaqi Wu
    • Liping Jiang
    • Tongtong Lv
    • Wenxi Liu
    • Jintong Zhang
    • Yanhua Zhang
    • Xiaochun Peng
    • Jie Tan
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The First Affiliated Hospital of Yangtze University, Jingzhou, Hubei 434023, P.R. China, Laboratory of Oncology, Center for Molecular Medicine, School of Basic Medicine, Health Science Center, Yangtze University, Jingzhou, Hubei 434023, P.R. China, Department of Oncology, The People's Hospital of Honghu, Jingzhou, Hubei 434023, P.R. China
  • Article Number: 98
    |
    Published online on: September 24, 2025
       https://doi.org/10.3892/ijo.2025.5804
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Abstract

Cancer prognostic assessment constitutes an essential component of cancer treatment and management. It encompasses the prediction of patients' disease progression, treatment effect and survival. Circulating free DNA (cfDNA) refers to highly fragmented DNA that exists extracellularly in the human bloodstream. Its methylation status is not only a reliable indicator for the prognosis of cancer, but also a highly accurate predictor of the prognosis of cancer. As an emerging non‑invasive biomarker, cfDNA has demonstrated considerable potential in cancer prognostic assessment in recent years. The present review provided a comprehensive review of the promising applications of cfDNA methylation in cancer prognostic assessment, while also discussing the challenges that must be addressed to fully realize its clinical potential. As technology advances and research deepens, cfDNA methylation is expected to play an increasingly pivotal role in the field of cancer precision medicine.
View Figures

Figure 1

Principle of cfDNA methylation
detection technology, as exemplified by cfDNA-RRBS. cfDNA-RRBS is a
methylation status analysis for cfDNA technology. This technique
combines restriction enzyme digestion and bisite sequencing to
detect and quantify methylation levels in cfDNA. The main steps are
Msp I digestion of cf A to enrich CpG dense regions. Then, it
undergoes bisulfite conversion. Bisulfite conversion is a chemical
process that converts unmethylated cytosine (C) to uracil (U),
while methylated cytosine remains unchanged (see the blue font part
in the figure), thereby distinguishing methylated and unmethylated
DNA. Finally, amplification and PCR amplification are carried out
using Random hexamer primer. CfDNA, circulating free DNA; RRBS,
reduced representation bisulfite sequencing.

Figure 2

Conventional prognostic assessment
methods for lung cancer and cancer diagnosis, imaging means such as
radiography, CT, MRI and PET-CT play a pivotal role, providing
strong support for accurate diagnosis. CT, computed tomography;
MRI, magnetic resonance imaging; PET-CT, positron emission
tomography and computed tomography; NSE, neuron-specific enolase;
CEA, carcinoembryonic antigen.
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Copy and paste a formatted citation
Spandidos Publications style
Su C, Wu J, Jiang L, Lv T, Liu W, Zhang J, Zhang Y, Peng X and Tan J: Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review). Int J Oncol 67: 98, 2025.
APA
Su, C., Wu, J., Jiang, L., Lv, T., Liu, W., Zhang, J. ... Tan, J. (2025). Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review). International Journal of Oncology, 67, 98. https://doi.org/10.3892/ijo.2025.5804
MLA
Su, C., Wu, J., Jiang, L., Lv, T., Liu, W., Zhang, J., Zhang, Y., Peng, X., Tan, J."Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review)". International Journal of Oncology 67.6 (2025): 98.
Chicago
Su, C., Wu, J., Jiang, L., Lv, T., Liu, W., Zhang, J., Zhang, Y., Peng, X., Tan, J."Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review)". International Journal of Oncology 67, no. 6 (2025): 98. https://doi.org/10.3892/ijo.2025.5804
Copy and paste a formatted citation
x
Spandidos Publications style
Su C, Wu J, Jiang L, Lv T, Liu W, Zhang J, Zhang Y, Peng X and Tan J: Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review). Int J Oncol 67: 98, 2025.
APA
Su, C., Wu, J., Jiang, L., Lv, T., Liu, W., Zhang, J. ... Tan, J. (2025). Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review). International Journal of Oncology, 67, 98. https://doi.org/10.3892/ijo.2025.5804
MLA
Su, C., Wu, J., Jiang, L., Lv, T., Liu, W., Zhang, J., Zhang, Y., Peng, X., Tan, J."Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review)". International Journal of Oncology 67.6 (2025): 98.
Chicago
Su, C., Wu, J., Jiang, L., Lv, T., Liu, W., Zhang, J., Zhang, Y., Peng, X., Tan, J."Application of cfDNA methylation in cancer prognostic assessment: Progress and challenges (Review)". International Journal of Oncology 67, no. 6 (2025): 98. https://doi.org/10.3892/ijo.2025.5804
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