Precision clinical medicine · 2026
Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma.
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Zhao Xinyu, Du Xingyi, Yang Shenqiao, Chen Su, Pu Chunlan, Fan Hengrui, Qiao Mingbiao, Yang Yi, Guo Yuanbiao, Guo Zhiyun
Аннотация
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.
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.