Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma

Abstract Objective Extrachromosomal circular DNA (eccDNA) contributes to tumorigenesis, but its role in tumor recurrence remains unclear. This study aimed to systematically characterize eccDNA profiles in recurrent and non-recurrent early-stage lung adenocarcinoma (LUAD) patients and evaluate their potential as prognostic biomarkers. Methods Tumor tissues, matched adjacent non-tumor tissues, and plasma were collected from patients with early-stage LUAD. All patients underwent a two-year postoperative follow-up to identify recurrence. Circle-seq and multi-omics analyses were applied to profile eccDNA landscapes in recurrent and non-recurrent patients. Results eccDNAs in recurrent LUAD patients exhibited significantly distinct features, including higher GC content, enhanced structural stability, increased expression levels, and enrichment in transcriptionally active regions. Recurrence-associated eccDNAs carry oncogenes and regulate pathways involved in tumor migration, invasion, and immune evasion via suppression of immune factor receptors. A recurrence risk model based on seven plasma eccDNA marker genes effectively stratified patients, with high-risk patients exhibiting significantly poorer disease-free survival. Conclusion These findings highlight the characteristics of eccDNAs in LUAD recurrence and their potential as prognostic biomarkers, providing preliminary multi-omics evidence for understanding the role of eccDNA in LUAD recurrence and laying the groundwork for future mechanistic studies and clinical translation.