Clinical application of plasma mitochondrial DNA content in patients with lung cancer

Abstract

Alterations of mitochondrial DNA (mtDNA) have been identified in several types of solid tumor. However, to the best of our knowledge, the clinical significance of plasma mtDNA content in lung cancer remains unknown. Thus, the current study explored the diagnostic and prognostic value of plasma mtDNA quantification in patients with lung cancer. Plasma mtDNA copy numbers of patients with lung cancer (n=128) and healthy individuals (n=107) were quantified by quantitative polymerase chain reaction. Plasma mtDNA copy numbers in patients and healthy controls were 0.89×104 and 1.37×104 copies/µl, respectively (P<0.0001). Furthermore, lower plasma mtDNA content was associated with tumor size, lymph node metastases, distant metastases and serum carcinoembryonic antigen levels (P<0.05), but was not associated with pathological type, age, sex or main driver gene mutation status (P>0.05). Plasma mtDNA facilitated the detection of lung cancer at a threshold of 1.19×104 copies/µl with a sensitivity of 71.1% and specificity of 70.1%, as determined by receiver operating characteristic curve analysis. Advanced stage (III and IV) patients with a lower mtDNA copy number (cutoff: 1.02×104 copies/µl) tended to exhibit poorer prognosis (P<0.05). These results indicated that plasma mtDNA content is a promising and complementary candidate with tissue mtDNA for diagnosis and prognostic prediction for lung cancer.

Involvement of Circulating Cell-Free Mitochondrial DNA and Proinflammatory Cytokines in Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

“…Increase of cf-MtDNA has been associated with COPD and, with some contradictory reports, lung cancer (Chen et al, 2018;Hou et al, 2019;Zhang et al, 2020). Results from our study show that the levels of cf-MtDNA in patients with COPD and NSCLC were significantly higher than that in the controls.…”

“…However, contradictory findings have been reported. For example, cf-MtDNA copy numbers in blood plasma were lower in patients with lung cancer than that in controls (Chen et al, 2018).…”

The Uprising of Mitochondrial DNA Biomarker in Cancer

“…A study suggested that mtDNA content analysis from peripheral blood could serve as a noninvasive biomarker and predictor for hepatocellular carcinoma risk in patients with hepatitis C [152]. Supported by other authors, their study used plasma and found it as a promising complementary sample alongside tissue specimens that served as a predictor for diagnosis and prognosis of lung cancer [154]. Several studies conducted in head and neck cancer areas showed significantly higher cf-mtDNA levels in cancer patients to be compared with control samples [155][156][157].…”

The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System

“…Moreover, the number of mtDNA copies have been correlated with different types of cancer. The decrease is reported for breast, liver, lung, and kidney cancers, while in prostate and head and neck cancers, excessive mtDNA copies are observed [199][200][201]. At the same time, cancer cell's mitochondria are considered as therapeutic targets, which may be a feature of personalized medicine in the future [202].…”