Specific circular DNA features found in blood and tissue could help clinicians identify patients at high risk for recurrence after surgery.
RT’s Three Key Takeaways:
- Prognostic DNA Markers: Researchers identified specific features of extrachromosomal circular DNA (eccDNA) that correlate with a higher risk of lung adenocarcinoma (LUAD) recurrence after surgery.
- Multi-Omics Risk Model: A new model based on seven plasma-derived genes consistently distinguished between high-risk and low-risk patients in terms of disease-free survival.
- Clinical Monitoring Potential: These findings suggest that eccDNA-based liquid biopsies could provide a non-invasive method for individualized postoperative risk assessment and monitoring in healthcare settings.
Researchers have identified specific extrachromosomal circular DNA (eccDNA) features that provide new prognostic insights for patients with lung adenocarcinoma (LUAD), according to a study published in Precision Clinical Medicine.
LUAD is the most common histological subtype of lung cancer. While surgery can be curative for patients diagnosed at an early stage, approximately 30% to 50% of patients develop recurrence or aggressive metastasis within five years. Because of this risk, researchers noted that more effective molecular markers are needed to improve postoperative risk assessment and follow-up in healthcare.
The study, 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, enrolled 90 treatment-naïve patients with early-stage LUAD. Researchers collected tumor tissue, matched adjacent non-tumor tissue, and plasma samples to investigate the genomic distribution and 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. These molecules were preferentially derived from transcriptionally active genomic regions and were associated with active histone modifications. Recurrence-associated eccDNAs carried several genes involved in cancer-related pathways, including mTOR, Notch, and Ras signaling, according to the researchers.
In plasma, the research team identified 2,387 eccDNAs that were commonly upregulated in lung cancer and recurrence-associated samples. By integrating genes linked to these signals with transcriptomic and survival data, the team selected seven genes—AFAP1L2, LHX8, IL20RB, SLC12A8, EGLN3, CDH3, and PLTP—to construct a recurrence risk model.
The model consistently distinguished patients with different disease-free survival (DFS) outcomes in both training and validation cohorts. These findings support the potential of eccDNA as a source of prognostic biomarkers, though researchers noted that further validation in larger prospective cohorts is needed to facilitate the development of eccDNA-based approaches for individualized postoperative risk assessment and monitoring.
