Abstract:
Circulating cell-free mitochondrial DNA (cf-MtDNA) has been reported in patients with chronic
obstructive pulmonary disease (COPD) and lung cancers. However, inter-relationships among the three biological
events have not been well-characterized. Therefore, our investigation was conducted to better understand the role
of cf-MtDNA on pathogenesis of the two diseases. Methods: Plasma samples were collected from 64 non-small
cell lung cancer (NSCLC) patients (before therapy), 45 patients with COPD and 62 healthy individuals. cf-MtDNA
copy numbers were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and cytokines were
determined using a human ELISA kit. Results: Our data indicate that smoking statuses of the patients and controls were
significantly associated with increased cf-MtDNA in plasma samples. Furthermore, NSCLC patients had significantly
higher cf-MtDNA copy numbers than COPD patients (p < 0.03) and normal controls (p < 0.02), together with elevated
proinflammatory cytokines over the controls (p < 0.05). Our study shows that the copy numbers for the NSCLC
patients were positively associated with their subsequent metastasis but inversely associated with their overall survival.
Conclusion: Our study indicates certain lung injury (e.g., from cigarette smoking) was responsible for the release of
cf-MtDNA and proinflammatory cytokines into plasmas among our patients and controls. The increase in cf-MtDNA
copy numbers was significantly associated with the development of both COPD and NSCLC, with increase in interleukin
6, and from our 5-year follow-up, with poor prognosis among the NSCLC patients. Therefore, with further validation,
cf-MtDNA can be considered for use as diagnostic and prognostic biomarkers for NSCLC.
