Emerging evidence has revealed that
mitochondrial DNA (
mtDNA) is encapsulated in plasma extracellular vesicles (EVs). However, the characteristics of
mtDNA in EVs from patients with
cancer remain largely unexplored, which greatly limits its clinical application. Whole genome and capture-based sequencing found that EV
mtDNA covered the whole mitochondrial genome. The medium fragment size in EV
mtDNA was significantly larger compared with that in cell-free
mtDNA [cfmtDNA; 159 vs. 109 base pairs (bp); P<0.001]. EV
DNA appeared to have a higher
mtDNA copy number compared with
cfDNA. Of note, patients with
hepatitis had >300-bp fragments in EV
mtDNA compared with patients with
hepatocellular carcinoma (HCC) and healthy controls. EV
mtDNA fragments >300 bp in length exhibited a significantly higher proportion of EV
mtDNA fragment ends than those that were ≤300 bp in length in patients with
hepatitis. The EV
mtDNA copy number in patients with HCC and
hepatitis were significantly lower compared with those in healthy controls. Furthermore, inconsistencies in the
mtDNA heteroplasmic variant were observed among HCC tissues, plasma and EVs. In conclusion, EV
mtDNA exhibited different characteristics among patients with HCC,
hepatitis and healthy controls, indicating the potential value of EV
mtDNA as a diagnostic
biomarker that complements cfmtDNA.