Study on Systemic and Airway Cytokines and Oxidative Stress in Lung Cancer Patients Undergoing Surgery

Lung cancer is the major cause of cancer deaths among both genders in Hong Kong. In 2005, primary lung cancer accounted for 33% and 25% of all cancer deaths in men and women respectively. On average, there are around 4,000 new cases of lung cancer each year. Non-small cell lung cancer (NSCLC) accounts for about 80% of all primary lung cancers. About 60% of cases present as advanced stages IIIB and IV disease. The currently available treatment modalities include surgery, radiotherapy and systemic chemotherapy. However, the overall prognosis remains dismal with 5-year survival rate less than 15%. Among those with early stage lung cancer, the 5-year survival rate is still suboptimal at around 60-70%. Therefore, there has been immense interest in the development of novel biomarkers to delineate the high risk group for subsequent tumour recurrence after curative lung resections. It has long been found that cellular prooxidant states promote cells to neoplastic growth, in part due to DNA damage caused by reactive oxygen species (ROS), i.e. superoxide anion and hydroxyl radical. The potential therapeutic role of antioxidants in the chemoprevention of lung cancer has therefore been brought to major clinical trials in recent years. Disappointingly, the major landmark chemoprevention trials including the Alpha-Tocopherol, Beta Carotene Cancer Prevention (ATBC) study and the Beta-Carotene and Retinol Efficacy Trial (CARET) have failed to demonstrate therapeutic benefits of vitamins A and E in lung cancer. Apart from the criticism about the dosages being used in the trials, these results may reflect the lack of understanding of the exact role of antioxidants in lung carcinogenesis. The simple use of general antioxidants, vitamins A and E, may not be able to target specifically the peculiar alterations in antioxidant profiles that lead to the development of lung cancer. In fact, our recent study has demonstrated specific changes in antioxidant expressions in surgically resected non-small cell lung cancer. In the resected lung cancer tissues, there were increased manganese superoxide dismutase (Mn SOD) and decreased catalase expressions at the transcriptional levels as compared with adjacent normal lung tissues. It has been hypothesized that this alteration in local antioxidant levels may result in anti-apoptosis and accumulation of genetic damages thus perpetuating carcinogenesis. However the exact clinical implications are still under investigation. Our previous case-control study on the systemic (erythrocyte) antioxidant activities in patients with NSCLC has shown an increased glutathione peroxidase (GPx), but decreased SOD activities compared with healthy controls. The erythrocyte SOD activity was associated with disease staging. In addition, our recent study on longitudinal profile of erythrocyte antioxidants during chemotherapy for advanced NSCLC has identified total glutathione as an independent predictor to treatment response, which may reflect tumour load (submitted, unpublished data).

Exhaled breath condensate (EBC) has recently emerged as a non-invasive sampling method for real-time analysis and evaluation of oxidative stress biomarkers in the lower respiratory tract airways, especially in various lung diseases including asthma, chronic obstructive pulmonary disease, and lung cancer. In particular, endothelin-1 and interleukin-6 have been found to be elevated in the EBC from patients with lung cancer. Therefore, the current study aims to evaluate the temporal changes of various oxidative stress biomarkers and cytokines in EBC and blood in patients with NSCLC who are undergoing surgical lung resections and the potential role of these parameters in predicting subsequent tumour recurrence. Also, the correlation of biomarkers in blood or EBC with lung tumour tissue will be looked into.