Cross Talk between Iron Regulatory Proteins and Proinflammatory Molecules in Ovarian Cancer Patients Based on Menopausal Status

Abstract

Micronutrient iron is postulated to contribute to the initiation of cancer mainly by the formation of Reactive Oxygen Species (ROS), the key signaling molecules of inflammatory reactions. Iron may also cause elevation of MMP9, a gelatinase responsible for remodeling extracellular matrix in cancer cells through the ROS pathway. Estrogen the hormone which decreases markedly in post menopause is also known to increase the risk of tumorigenesis in ovaries. Hence this study aims to explore alterations in iron metabolism in Ovarian Cancer (OC) patients based on menopausal status. Plasma iron, Total Iron Binding Capacity (TIBC), erythropoietin and ceruloplasmin were estimated spectrophotometrically in 33 premenopausal and 50 postmenopausal OC patients. Proinflammatory cytokine TNFα and MMP9 were determined by ELISA. Plasma iron was markedly lower and erythropoietin was significantly higher in all OC patients compared to normal reference intervals, irrespective of menopausal state indicating severe anemia in OC. TIBC was significantly lower in postmenopausal OC patients compared to their premenopausal counterparts (p = 0.023). Plasma ceruloplasmin was significantly higher in postmenopausal OC patients compared to premenopausal patients (p = 0.022), implying greater oxidative stress. The increase in TNFα was statistically significant in postmenopausal cancer patients compared to their premenopausal counterparts (p = 0.005). A substantial increase in MMP9 suggests the enhanced ability of tumor cells for migration and invasion in postmenopausal OC patients. The results of the present study demonstrate greatly perturbed iron metabolism in postmenopausal OC patients than in premenopausal patients. This higher degree of iron dysregulation may induce persistent ROS production and promote inflammatory processes in OC.