ArticleClinical epigenetics2025
Genome-wide methylation analysis of circulating cell-free DNA identifies an episignature in lung cancer: validation of EMP2 as a potential biomarker.
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 2 papers.
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Who cites it
2 citing papers in PubMed.
- Biological basis and clinical translation prospects of circulating cell-free DNA in precision management of breast cancer (Review).Oncology letters · 2026Review
- Epigenetic profiling of circulating cell-free DNA for early detection and minimal residual disease assessment in lung cancer: a focus on DNA methylation.Frontiers in oncology · 2026Review
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Authors and funding
13 authors.
Funding
Abstract
backgroundLung cancer (LC) remains the leading cause of cancer-related mortality worldwide. Its poor prognosis is largely attributed to late-stage diagnosis, highlighting the need for sensitive, minimally invasive biomarkers for early detection. In this study, we aimed to identify circulating cell-free DNA (cfDNA) methylation-based biomarkers for LC through genome-wide profiling of plasma-derived cfDNA from patients with LC (stages I-IV) using the Infinium DNA MethylationEPIC array (> 850,000 CpGs). A relaxed elastic net penalized logistic regression model was applied to identify differentially methylated CpGs between LC patients and non-neoplastic controls, and selected candidates were validated in an independent cohort.
resultsA 21-CpG episignature was identified, predominantly hypomethylated in LC, which distinguished cases (n = 25) from controls (n = 8) with a cross-validated area under the curve (AUC) of 0.70. Two CpGs with the largest effect sizes (associated with EMP2 and IKZF2) were selected for validation. Digital droplet PCR (ddPCR) analysis in an independent cohort of 47 individuals (23 LC patients and 24 controls) confirmed significant hypomethylation at the EMP2 locus (median % methylation: 73.60% in tumors vs. 86.83% in controls; p = 0.0034), achieving an AUC of 0.75.
conclusionsOur findings support the utility of methylome-wide cfDNA profiling for LC biomarker discovery. EMP2 promoter methylation represents a promising candidate for the minimally invasive detection of LC across heterogeneous clinical presentations.
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