Liquid biopsies using pleural effusion-derived exosomal DNA in advanced lung adenocarcinoma

Background: Recently, plasma-derived exosomal DNA (exoDNA) has been successfully used in clinical genetic testing. However, the clinical utility of pleural effusion-derived exoDNA (PE-exoDNA) was still unknown. This study aimed to assess the feasibility of using PE-exoDNA for genetic testing in patients with advanced lung adenocarcinoma. Methods: Twenty PE-exoDNA samples and 18 pleural effusion-derived cell-free DNA (PE-cfDNA) samples were obtained from 20 stage IV lung adenocarcinoma patients. Using targeted next-generation sequencing (NGS) of 416 cancer-relevant genes, the genomic alterations between PE-exoDNA and PE-cfDNA were identified and compared. Results: NGS results showed highly similar mutation profiles between exoDNA and cfDNA, with TP53, EGFR, PKD1, and ALK as the top 4 mutated genes in both samples. A total of 304 genetic mutations were identified in 18 cfDNA samples and 276 genetic mutations were identified in 20 exoDNA samples. Forty-seven mutations from 8 genes (EGFR, ALK, KARS, BRAF, MET, PTEN, TP53, and RB1) were identified in 18 patients who had both exoDNA and cfDNA samples. Of the 47 mutations, 43 were shared between the two types of samples, yielding a concordance rate of 89.6%. Collectively, 78% of the mutations were shared between exoDNA and cfDNA samples, and this frequency increased to 94.2% when copy number variations (CNVs) were excluded from the analysis. Conclusions: In patients with advanced lung adenocarcinoma, the genetic profile of PE-exoDNA and PE-cfDNA were comparable, except for CNVs that had lower similarities between these two samples. Our findings support the clinical utility of exoDNA and could motivate further exploration of using exoDNA as an alternative source for genetic testing.