Scholarlink

Background <p>Lung 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 (&gt; 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.</p> Results <p>A 21-CpG episignature was identified, predominantly hypomethylated in LC, which distinguished cases (<i>n</i> = 25) from controls (<i>n</i> = 8) with a cross-validated area under the curve (AUC) of 0.70. Two CpGs with the largest effect sizes (associated with <i>EMP2</i> and <i>IKZF2</i>) 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 <i>EMP2</i> locus (median % methylation: 73.60% in tumors vs. 86.83% in controls; <i>p</i> = 0.0034), achieving an AUC of 0.75.</p> Conclusions <p>Our findings support the utility of methylome-wide cfDNA profiling for LC biomarker discovery. <i>EMP2</i> promoter methylation represents a promising candidate for the minimally invasive detection of LC across heterogeneous clinical presentations.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genome-wide methylation analysis of circulating cell-free DNA identifies an episignature in lung cancer: validation of EMP2 as a potential biomarker

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月2日

查看全文
  • Ester Alemany-Cosme,
  • Dario Cruz-Chamorro,
  • David Hervas,
  • Diana Garcia,
  • Raquel Martinez-Tomas,
  • Andres Briones-Gomez,
  • Jose Galbis-Caravajal,
  • Alfonso Calvo,
  • Oscar Juan,
  • Agustin Lahoz,
  • Enrique Cases,
  • Cora Palanca-Ballester,
  • Juan Sandoval

摘要

Background

Lung 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.

Results

A 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.

Conclusions

Our 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.