ArticleClinical epigenetics2025
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.
Article in Clinical epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Methylated circulating tumor DNA: technical challenges and clinical applications in non-small cell lung cancer patients-a narrative review.Translational lung cancer research · 2026Review
- Liquid biopsies for detection, characterization, and interception of therapy resistance in thoracic malignancies.Frontiers in oncology · 2026Review
- Review
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Authors and funding
31 authors.
Funding
Abstract
backgroundThe present study aimed to clarify the clinical significance of the cell-free DNA (cfDNA) methylation profile of patients with non-small cell lung cancer (NSCLC) showing the epidermal growth factor receptor (EGFR) gene mutation.
methodsIn 103 patients, genome-wide DNA methylation analysis using Infinium Methylation EPIC array was performed using samples of pre-tyrosine kinase inhibitor afatinib-treatment plasma cfDNA (n = 101) and post-afatinib cfDNA (n = 84).
resultsPrincipal component analysis indicated that the cfDNA methylation profile was altered after afatinib treatment. Hierarchical clustering using the pre-afatinib cfDNA methylation profile revealed that cases with a fatal outcome were accumulated in specific clusters. Moreover, Kaplan-Meier analysis showed that the pre-afatinib cfDNA methylation profile was significantly associated with both progression-free survival (PFS) and overall survival (OS), whereas the post-afatinib profile was not. 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. Using the cfDNA methylation levels at two CpG sites, cg12721600 and cg05905155, patients showing an overall response were predicted with a sensitivity of 96% or more.
conclusionsThe 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.
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