Circular eccDNA Features Offer New Prognostic Insights for Early-Stage Lung Adenocarcinoma Recurrence
核心洞察
A multi-omics study of 90 treatment-naïve early-stage LUAD patients reveals that recurrence-associated eccDNAs exhibit distinct features including higher GC content and stronger split-read signals compared to non-recurrent tumors.
Recurrence-associated eccDNAs were preferentially derived from transcriptionally active genomic regions and carried genes involved in mTOR, Notch, and Ras signaling pathways.
Researchers identified 2,387 plasma eccDNAs commonly upregulated in lung cancer and recurrence-associated samples, leading to a seven-gene recurrence risk model.
A new study published in Precision Clinical Medicine provides a comprehensive multi-omics characterization of extrachromosomal circular DNA (eccDNA) in early-stage lung adenocarcinoma (搜索) (LUAD), revealing distinct molecular features associated with postoperative recurrence and offering a potential blood-based prognostic tool.
LUAD, the most common histological subtype of lung cancer, presents a significant clinical challenge: 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.
The study, published on 6 July 2026 (DOI: 10.1093/pcmedi/pbag017), was conducted by researchers from Southwest Jiaotong University (搜索), The Third People's Hospital of Chengdu (搜索), Chengdu University of Traditional Chinese Medicine (搜索), and Deyang People's Hospital (搜索).
Distinct Genomic Features of Recurrence-Associated eccDNA
The researchers enrolled 90 treatment-naïve patients with early-stage LUAD and collected tumor tissue, matched adjacent non-tumor tissue, and plasma samples. Using Circle-seq and public multi-omics datasets, they investigated the genomic distribution, transcriptional activity, chromatin characteristics, and potential clinical relevance of eccDNA.
The results demonstrated that eccDNAs from recurrent tumors exhibited higher GC content and stronger split-read signals compared with those from non-recurrent tumors. These recurrence-associated eccDNAs were preferentially derived from transcriptionally active genomic regions, including exons, CpG islands, and chromatin A compartments, and were associated with active histone modifications.
Cancer Pathway Involvement and Immune Signaling
Recurrence-associated eccDNAs were found to carry several genes involved in cancer-related pathways, including mTOR, Notch, and Ras signaling. Additionally, differences were 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.
A Seven-Gene Plasma-Based Recurrence Risk Model
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 (搜索), LHX8 (搜索), IL20RB (搜索), SLC12A8 (搜索), EGLN3 (搜索), CDH3 (搜索), and PLTP (搜索)—for construction of a recurrence risk model.
The model consistently distinguished patients with different disease-free survival (DFS) outcomes in both training and validation cohorts. 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, potentially addressing a critical unmet need in the management of early-stage lung adenocarcinoma (搜索).