Loyola University Medical Center, Maywood, IL
Srdjan Nikolovski , Mark Jaradeh , Fakiha Siddiqui , Jeanine Walenga , Walter Jeske , Jawed Fareed , Wickii T. Vigneswaran
Background: Interplay between oxidative stress and inflammation play major role in the development and progression of various malignancies. As one of the most common and the deadliest malignancy, lung cancer has a prominent vicious cycle of oxidative stress and immune response. The aim of this study is to examine the inter-relationship between basic oxidative stress and inflammation-related plasma biomarkers in patients with non-small cell lung cancer (NSCLC) undergoing surgical resection procedure. Methods: After obtaining informed consent, pre-operative plasma levels of alpha-fetoprotein, nitrotyrosine, urokinase-type plasminogen activator, and myeloperoxidase (MPO) as oxidative stress-related biomarkers were determined in 49 patients with diagnosed NSCLC. In the same patient group, plasma levels of interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), interferon gamma, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and epidermal growth factor were also evaluated. Control samples were obtained from 34 healthy individuals. Plasma biomarkers were determined by enzyme-linked immunosorbent assay. Applicable statistical methods were used to analyze the data. Results: Positive correlation was observed between MPO and levels of the following inflammation-related biomarkers: IL-6 (r = 0.397, p = 0.007), VEGF (r = 0.494, p = 0.001), TNF-α (r = 0.348, p = 0.019), and MCP-1 (r = 0.377, p = 0.011). Biomarkers showing significance in correlation analysis were further analyzed by linear logistic regression in order to determine presence and strength of causality in each direction (oxidative stress to inflammation and inflammation to oxidative stress). IL-6 and VEGF were observed as a predictors of MPO levels (B = 0.334, p = 0.031, and B = 0.391, p = 0.039, respectively). Furthermore, causality was observed in the opposite direction as well. MPO levels were shown as a slightly better predictor of both IL-6 and VEGF plasma levels (B = 0.349, p = 0.007, and B = 0.433, p = 0.001, respectively), but also as a predictor of TNF-α and MCP-1 levels (B = 0.193, p = 0.019, and B = 0.217, p = 0.011, respectively). Conclusions: Conclusion: These studies showed a strong correlation between measured oxidative stress-related and inflammatory biomarkers. Furthermore, these observations underscore the importance of oxidative stress in the pathogenesis of lung cancer.
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