A multi-omics study has revealed distinct extrachromosomal circular DNA (eccDNA) features associated with postoperative recurrence in lung adenocarcinoma (LUAD). By integrating Circle-seq with genomic, transcriptomic, epigenomic, and clinical data, the researchers characterized recurrence-associated eccDNA profiles and identified a seven-gene signature with potential value for recurrence risk stratification.
LUAD is the most common histological subtype of lung cancer. Although surgery can be curative for patients diagnosed at an early stage, approximately 30%–50% develop recurrence or aggressive metastasis within five years. More effective molecular markers are therefore needed to improve postoperative risk assessment and follow-up. eccDNA is a class of circular double-stranded DNA molecules that exists independently of chromosomes and can be detected in both tumor tissue and plasma. Its involvement in tumor evolution, heterogeneity, metastasis, and treatment resistance has attracted growing interest, but the characteristics of eccDNA associated with early-stage LUAD recurrence remain incompletely understood.
Published in Precision Clinical Medicine on 6 July 2026 (DOI: 10.1093/pcmedi/pbag017) , the study was conducted by researchers from Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu University of Traditional Chinese Medicine, and Deyang People’s Hospital. The study enrolled 90 treatment-naïve patients with early-stage LUAD and collected tumor tissue, matched adjacent non-tumor tissue, and plasma samples. Circle-seq and public multi-omics datasets were subsequently integrated to investigate the genomic distribution, transcriptional activity, chromatin characteristics, and potential clinical relevance of eccDNA.
The results showed that eccDNAs from recurrent tumors had higher GC content and stronger split-read signals than those from non-recurrent tumors. They were also preferentially derived from transcriptionally active genomic regions, including exons, CpG islands, and chromatin A compartments, and were associated with active histone modifications. Recurrence-associated eccDNAs carried several genes involved in cancer-related pathways, including mTOR, Notch, and Ras signaling. Differences were also observed in the expression of eccDNA-associated immune factors and their receptors, suggesting a possible relationship between eccDNA and altered immune signaling in recurrent LUAD.
In plasma, the researchers identified 2,387 eccDNAs that were commonly upregulated in lung cancer and recurrence-associated samples. Genes linked to these plasma eccDNA signals were integrated with public transcriptomic and survival data, leading to the selection of seven genes—AFAP1L2, LHX8, IL20RB, SLC12A8, EGLN3, CDH3, and PLTP—for construction of a recurrence risk model. The model consistently distinguished patients with different DFS(disease-free survival) outcomes in both training and validation cohorts. Together, these findings provide a multi-omics view of recurrence-associated eccDNA in LUAD and support its potential as a source of prognostic biomarkers. Further validation in larger prospective cohorts may facilitate the development of eccDNA-based approaches for individualized postoperative risk assessment and monitoring.
###
References
DOI
Original Source URL
https://doi.org/10.1093/pcmedi/pbag017
Funding information
This work was supported by the Key Research and Development Program of the Department of Science and Technology of Sichuan Province (grant No. 2024YFFK0332), the Basic Research Cultivation Support Program of Fundamental Research Funds for the Central Universities (grant No. 2682023ZTPY071), and the Sichuan Province Science and Technology Support Program (grant No. 2022NSFSC0779).
About Precision Clinical Medicine
Precision Clinical Medicine (PCM) commits itself to the combination of precision medical research and clinical application. PCM is an international, peer-reviewed, open-access journal that publishes original research articles, reviews, clinical trials, methodologies, opinions in the field of precision medicine in a timely manner. By doing so, the journal aims to provide new theories, methods, and evidence for disease diagnosis, treatment, prevention and prognosis, so as to establish a communication platform for clinicians and researchers that will impact practice of medicine. The journal covers all aspects of precision medicine, which uses novel means of diagnosis, treatment and prevention tailored to the needs of a patient or a sub-group of patients based on the specific genetic, phenotypic, or psychosocial characteristics. Clinical conditions include cancer, infectious disease, inherited diseases, complex diseases, rare diseases, etc. The journal is now indexed in ESCI, Scopus, PubMed Central, etc., with an impact factor of 6.4 (JCR2025, Q1). For further information, please refer to the journal homepage: https://academic.oup.com/pcm .
Precision Clinical Medicine
Not applicable
Multi-omics profiling of recurrence-associated extrachromosomal circular DNA characteristics and its prognostic potential in lung adenocarcinoma
6-Jul-2026
The authors declare that they have no competing interests.