Redox Imbalance in Lung Cancer of Patients with Underlying Chronic Respiratory Conditions

Abstract

Chronic respiratory diseases such as obstructive pulmonary disease (COPD) and oxidative stress may underlie lung cancer (LC). We hypothesized that the profile of oxidative and antioxidant events may differ in lung tumors and blood compartments of patients with non-small cell LC (NSCLC) with and without COPD. Redox markers (immunoblotting, ELISA, chemiluminescence, 2D electrophoresis and proteomics) were analyzed in blood samples of 17 control subjects and 80 LC patients (59 LC-COPD and 21 LC) and lung specimens (tumor and nontumor) from those undergoing thoracotomy (35 patients: 23 LC-COPD and 12 LC). As smoking history was more prevalent in LC-COPD patients, these were further analyzed post hoc as heavy and moderate smokers (cutoff, 60 pack-years). Malondialdehyde (MDA)-protein adducts and SOD1 levels were higher in tumor and nontumor samples of LC-COPD than in LC. In tumors compared with nontumors, SOD2 protein content was greater, whereas catalase levels were decreased in both LC and LC-COPD patients. Blood superoxide anion levels, protein carbonylation and nitration were greater in LC and LC-COPD patients than in the controls, and in the latter patients compared with the former. Systemic superoxide anion, protein carbonyls and nitrotyrosine above specific cutoff values best identified underlying COPD among all patients. Smoking did not influence the study results. A differential expression profile of oxidative stress markers exists in blood and, to a lesser extent, in the tumors of LC-COPD patients. These findings suggest that systemic oxidative stress and lung antioxidants (potential biomarkers) may predispose patients with chronic respiratory diseases to a higher risk for LC.

Oxidant status, iron homeostasis, and carotenoid levels of COPD patients with advanced disease and LTOT

“…In the present study, we used PC in plasma as an index for systemic oxidative status, but could, however, not find any significant difference between controls and COPD subjects. Other research groups have shown a significant difference using PC in plasma, but these studies were larger than the present study [27,28]. …”

Relationships between chronic obstructive pulmonary disease and lung cancer: biological insights

“…Oxidative stress, defined as the imbalance between oxidants and antioxidants in favor of the former, represents another relevant contributing factor to LC progression (18)(19)(20)(21)(22)(25)(26)(27)(28)33,36) ( Figure 3). Oxidative and nitrosative stress were shown to favor carcinogenesis through the activation of cellular processes that result in neoplastic transformation, the induction of DNA mutations (32,114), or even through induction of macrophage dysfunction (alterations in phagocytosis) (27).…”

“…Several structural and functional proteins were significantly more oxidized in the lung tumors and nontumor parenchyma in patients with LC (26). In fact, proteins such as cofilin (34), vimentin (115), and alpha-1-antitrypsin (116,117) were also shown to be more oxidized in the normal epithelium of the airways distant to the neoplasm in patients with LC (25), and their function was altered as a result of the oxidative posttranslational modifications, which may contribute to lung destruction and emphysema (116,117).…”

“…The study of the underlying biological mechanisms that may predispose patients with chronic respiratory diseases to a higher incidence of LC has also gained much attention in the last few years by several investigators including those listed in this review (25)(26)(27)(28)(29)(30)(31). For instance, oxidative and nitrosative stress as a result of reactive oxygen and nitrogen species (ROS and RNS, respectively) were shown to favor carcinogenesis through the activation of cellular processes that result in neoplastic transformation or the induction of DNA mutations (32).…”

“…For instance, oxidative and nitrosative stress as a result of reactive oxygen and nitrogen species (ROS and RNS, respectively) were shown to favor carcinogenesis through the activation of cellular processes that result in neoplastic transformation or the induction of DNA mutations (32). Other investigations have also demonstrated the contribution of oxidative damage, inflammatory events, and tumor microenvironment to lung carcinogenesis in patients and animal models (19,20,(25)(26)(27)(28)(29)(30)(31)(33)(34)(35)(36)(37).…”