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Genetic research

Plasma Cell-Free DNA Methylation Profile Predicts Non-Small Cell Lung Cancer Outcomes

Strategic Insights

— 2 min read

New research has shed light on the potential use of cell-free DNA (cfDNA) methylation profiles to predict outcomes in non-small cell lung cancer (NSCLC) patients treated with afatinib. The study, conducted at Keio University School of Medicine, analyzed the cfDNA methylation profiles of 103 patients with NSCLC and found that the pre-afatinib cfDNA methylation profile was significantly associated with both progression-free survival (PFS) and overall survival (OS). The researchers also identified specific genes and pathways that were associated with PFS and OS, including the cadherin, Wnt, and EGFR signaling pathways.

Key Takeaways:

  • The pre-afatinib cfDNA methylation profile was significantly associated with both PFS and OS in patients with NSCLC.
  • The genes for which pre-afatinib cfDNA methylation levels were associated with PFS were accumulated in the cadherin, Wnt, and EGFR signaling pathways.
  • Activation of EGFR-related signaling due to DNA methylation alterations might overturn the effect of afatinib.
  • Pre-afatinib levels of CEP170 and CHCHD6 cfDNA methylation were associated with both PFS and OS.
  • Both pre- and post-afatinib cfDNA methylation levels of SLC9A3R2 and INTS1 were associated with bone metastasis.
  • The non-invasively measurable cfDNA methylation profile may reflect the corresponding profile in cancer cells, and that pre-treatment measurement may provide clinically useful information on EGFR mutation-positive NSCLC.

Statistics:

  • 103 patients with NSCLC were included in the study.
  • The study analyzed the cfDNA methylation profiles of pre-afatinib treatment plasma samples (n = 101).
  • The study analyzed the cfDNA methylation profiles of post-afatinib treatment plasma samples (n = 84).
  • The pre-afatinib cfDNA methylation profile was significantly associated with PFS (p < 0.001).
  • The pre-afatinib cfDNA methylation profile was significantly associated with OS (p < 0.001).
  • The sensitivity of predicting an overall response using the cfDNA methylation levels at two CpG sites, cg12721600 and cg05905155, was 96% or more.

Sources:

  • NewsRx. Research from Keio University School of Medicine in the Area of Non-Small Cell Lung Cancer Published (Plasma cell-free DNA methylation profile before afatinib treatment is associated with progression-free and overall survival of patients with ...). Health & Medicine Week. May 16, 2025; p 5371.
  • Fujimoto, M., Yasuda, H., Arai, E., Nakajima, M., Takata, S., Morikawa, K., ... & Togashi, A. (2025). Plasma cell-free DNA methylation profile before afatinib treatment is associated with progression-free and overall survival of patients with epidermal growth factor receptor gene mutation-positive non-small cell lung cancer. Clinical Epigenetics, 17(1), 1-14. (DOI: 10.1186/s13148-025-01870-8)
  • Clinical Epigenetics - http://www.clinicalepigeneticsjournal.com/
  • BMC - publisher for Clinical Epigenetics.
  • https://doi-org.sdpl.idm.oclc.org/10.1186/s13148-025-01870-8

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