Association Between NOX۴ And Nrf۲ Genes in Non-Small-Cell Lung Carcinoma: A Case-Control Study

Background: Epithelial malignancy in lung cancer, which is initiated with myofibroblast differentiation and remodeling, promotes hypoxia and intracellular ROS generation most affected by the prototypical enzyme, NADPH oxidase ۴ (NOX۴). In addition, nuclear factor erythroid ۲-related factor ۲ (Nrf۲) acts as a critical transcription factor by stimulating antioxidant proteins as redox homeostasis regulators. The aim of this study was to investigate a possible correlation between lung tissue NOX۴ and Nrf۲ genes (NOX۴ and Nrf۲) mRNA expression and bronchoalveolar lavage fluid (BALF) protein expression in non-small-cell lung carcinoma (NSCLC) patients. Methods: Samples from ۲۵ patients with various NSCLC types and stages and ۲۰ healthy controls were collected. NOX۴ and Nrf۲ mRNA were measured by qRT-PCR, and protein by western blot analysis. Results: NOX۴ mRNA and protein expression was significantly up-regulated in NSCLC patients’ lung tissues and BALFs (p= ۰.۰۳ and ۰.۰۱, respectively). In addition, by adjusting for age, sex, and NSCLC types and stages, a significant and positive correlation was observed between NOX۴ and Nrf۲ mRNA expression (r= ۰.۹۲۷, p= ۰.۰۰۱). This was also true when not adjusted as above (r= ۰.۹۴۴, p< ۰.۰۰۱). Conclusions: NOX۴ mRNA and protein expression is significantly up-regulated in NSCLC patients’ lung tissues and BALFs, and NOX۴ and Nrf۲ mRNA expression is positively correlated in NSCLC tissues.  

Keywords:

Gene expression , Non-small-cell lung cancer , NOX۴ , Nrf۲.