The mtDNA fragments within exosomes might be novel diagnostic biomarkers of non-small cell lung cancer

Abstract

Background: A portion of circulating mtDNAs is encapsulated in exosomes, but their contribution to cancers is rarely studied. We aim to investigate the diagnostic potential of exosomal mtDNA content for non-small cell lung cancer (NSCLC).

Methods: Exosomes were isolated from plasma and identified by western blot, scanning electron microscopy, and particle size analysis. The plasma and plasma exosomal mtDNA fragment levels (mtDNA79, mtDNA230, and MTATP8) in healthy, pneumonia, benign lung tumors, and NSCLC were quantified by qPCR. Statistical analyses were performed to compare the levels of mtDNA fragments in different subgroups. ROC analyses were used to evaluate mtDNA fragments' diagnostic sensitivity and specificity.

Results: We found that plasma mtDNAs were partially present in exosomes. Both plasma and exosomal mtDNA fragments (mtDNA79, mtDNA230, and MTATP8) were increased in NSCLC, particularly more malignant NSCLC. Compared to plasma mtDNAs and traditional tumor markers, exosomal mtDNAs are more closely associated with aggressive features of NSCLC, like bigger tumor sizes, advanced stages, lymph node metastasis, and distant metastasis, showing higher sensitivity and specificity to diagnose NSCLC.

Conclusions: Changed contents of plasma and plasma exosomal mtDNAs show great potential to diagnose NSCLC, and exosomal mtDNAs might be promising biomarkers for more aggressive NSCLC.

Keywords: Diagnosis; Exosomes; Mitochondrial DNAs; Non-small cell lung cancer; Tumor markers.