Abstract

Objective: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.

Highlights

  • Chronic obstructive pulmonary disease (COPD) and lung cancer are two of the major chronic diseases in many countries around the world, including Kazakhstan (World Health Organization, 2020) [https://www.who. int/news/item/09-12-2020-who-reveals-leading-causesof-death-and-disability-worldwide-2000-2019]

  • Plasma samples were collected from 64 non-small cell lung cancer (NSCLC) patients, 45 patients with chronic obstructive pulmonary disease (COPD) and 62 healthy individuals. cf-MtDNA copy numbers were detected using quantitative real-time polymerase chain reaction and cytokines were determined using a human ELISA kit

  • 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

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Summary

Introduction

Chronic obstructive pulmonary disease (COPD) and lung cancer are two of the major chronic diseases in many countries around the world, including Kazakhstan (World Health Organization, 2020) [https://www.who. int/news/item/09-12-2020-who-reveals-leading-causesof-death-and-disability-worldwide-2000-2019]. Chronic obstructive pulmonary disease (COPD) and lung cancer are two of the major chronic diseases in many countries around the world, including Kazakhstan (World Health Organization, 2020) [https://www.who. Cigarette smoking is well-recognized to be a major contributing factor to both diseases, especially for non-small cell lung cancer (NSCLC). COPD has been reported to be an independent risk factor for NSCLC, there are NSCLC cases without any history of COPD (Tang et al, 2020). Such scenario has created opportunities for investigations on mechanistic relationships between COPD and NSCLC, especially on identifying new biomarkers which can be used to identify the diseases and to provide prognostic values. Our investigation was focused onto characterizing the usefulness of circulating cell-free mitochondrial DNA (cf-MtDNA) and cytokines for COPD and NSCLC

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