Abstract
Oxidative stress induced by tobacco smoking is one of the main causes of DNA damage and is known to be involved in various cancers. Smoking is the leading cause of lung cancer, while the role of cigarette smoke-induced oxidative DNA damage response during lung carcinogenesis is largely unknown. In this study, we investigated oxidative DNA damage response levels in smoking and nonsmoking patients with lung cancer, and evaluated the potential diagnostic value of 8-OHdG for lung cancer. We observed a higher level of 8-OHdG expression and secretion in airways of lung cancer patients than that of noncancer controls. 8-OHdG expression was associated with the TNM stages. Additionally, cigarette smoke-induced oxidative DNA damage response was observed in bronchial epithelial cells in vitro and in vivo. A statistical significance correlation was found between the levels of 8-OHdG and smoking index. With a cut-off value of 2.86 ng/ml, 8-OHdG showed a sensitivity and specificity of 70.0% and 73.7%, respectively, to identify a patient with lung cancer. These findings not only underscore the importance of smoking in oxidative DNA damage response of lung cancer patients, but also suggest 8-OHdG as a potential diagnostic biomarker for lung cancer.
Highlights
Lung cancer is one of the most common form of malignant diseases and the leading cause of cancer-related mortality worldwide [1]
To demonstrate cigarette smoke-induced oxidative DNA damage response in bronchial epithelial cells, we first detected the expression of 8-OHdG in HBE cells after treated with cigarette smoke extract (CSE) (Figure 1A)
The present study showed a higher 8-OHdG expression and secretion in airways of lung cancer patients than that of noncancer controls, which was agreed with previous findings in peripheral blood and urinary [21,22,23]
Summary
Lung cancer is one of the most common form of malignant diseases and the leading cause of cancer-related mortality worldwide [1]. It is reported that approximately two-thirds of lung cancer patients is the presence of advance disease at the time of diagnosis [2]. Novel lung cancer diagnostic tests, which can be used to screen individuals at high risk, are required. Numerous studies have been conducted to investigate the usefulness of serum biomarkers for differential diagnosis of lung cancer. Biomarkers testing in BALF may be more useful than that in serum for lung cancer [5,6,7,8,9,10]
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