Global characterization of extrachromosomal circular DNA in cerebrospinal fluid of lung adenocarcinoma

Non-small cell lung cancer (NSCLC) is a particularly aggressive subtype of lung cancer characterized by early metastasis and poor prognosis. Lung adenocarcinoma (LUAD) represents the most prevalent histological subtype within NSCLC. The development of brain metastases in LUAD is frequently associated with a severely unfavorable outcome. While extrachromosomal circular DNA (eccDNA) has been implicated in various tumors, its specific role in brain metastasis related to LUAD remains largely unexplored.

EccDNA associated with brain metastasis in LUAD profiles was collected through sequencing 20 cerebrospinal fluid (CSF) samples from both control subjects and LUAD patients with brain metastases, focusing on those with Epidermal Growth Factor Receptor (EGFR) mutations, rare mutations, or no mutations at all. The genomic characteristics of the eccDNAs were examined across groups utilizing a circular map. Differentially expressed eccDNAs were subjected to analysis and functional annotation by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), employing eccDNA-related genes.

The distribution of eccDNAs within the genome is intricately associated with gene density. We compared the genomic features of eccDNAs between the subtypes of control and brain metastatic LUAD. Differentially expressed eccDNAs in CSF were identified, and subsequent GO and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses demonstrated their functional relevance in each group.

Our findings offer initial insights into the features of CSF-enriched eccDNAs across LUAD subtypes with varying pathogenic mechanisms, emphasizing their potential as diagnostic and prognostic indicators for LUAD.