Plasma extrachromosomal circular DNA as a biomarker in EGFR-targeted therapy of non-small cell lung cancer.

The genomic instability associated with cancer can result in the formation of extrachromosomal circular DNA (eccDNA), which contributes to tumor heterogeneity, gene amplification, tumor evolution, and drug resistance. However, most studies on eccDNA have been conducted on tumor tissue or cancer cell lines, and limited research has been done on eccDNA in plasma. In this study, we investigated eccDNA in non-small cell lung cancer (NSCLC) by sequencing plasma eccDNA from 32 epidermal growth factor receptor (EGFR)-mutated NSCLC patients before and during treatment with osimertinib, as well as plasma eccDNA from five healthy individuals. Plasma eccDNA was identified in all samples but with significantly higher levels in cancer patients than healthy controls. EGFR-overlapping eccDNA, eccDNA that contains part of or the whole EGFR gene, was detected in the majority of samples both at baseline and during treatment. High levels of EGFR-overlapping eccDNA during osimertinib treatment were associated with significantly shorter progression-free survival and overall survival. Plasma eccDNA represents a newly identified type of biomarker for monitoring treatment efficacy.