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

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 2-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.