Interplay of iron regulatory proteins and inflammatory markers in benign and malignant ovarian cancer: A cross sectional study.

Background: A wide array of alterations in the metabolism of iron makes it the most crucial micronutrient needed for cancer proliferation, mainly by generating oxygen derived free radicals, the key signalling molecules of inflammatory processes. Inflammation in turn induces iron sequestration by macrophages resulting in reduction of circulating iron for erythropoiesis. Iron may also facilitate metastasis by elevation of matrix metalloproteinases (MMP) responsible for remodelling of extracellular matrix through the ROS pathway. Hence, the aim of the study is to investigate alterations in the interplay of proteins that regulate iron homeostasis and inflammation in benign and malignant ovarian cancer (OC) patients. Materials and methods: Plasma ceruloplasmin, total iron binding capacity (TIBC), erythropoietin and iron were analysed by spectrophotometric methods in 33 cystadenoma and 50 adenocarcinoma OC patients. Plasma TNFα and MMP9 the proinflammatory molecules were estimated by ELISA. Results: Plasma iron levels were markedly reduced, whereas erythropoietin and TIBC were elevated in both benign and malignant cancer patients compared to normal reference intervals, indicating severe anemia irrespective of tumor type. The rise in erythropoietin was significantly greater in benign cases than malignant (p=0.012). TIBC increased progressively from normal mean value of 80µg/ dl to 102 in benign and 113 in malignant cancer. Plasma ceruloplasmin, a powerful antioxidant and a ferroxidase was significantly higher in malignant OC patients compared to benign group (p=0.001). While there was a substantial increase in MMP9 in OC patients, strikingly higher values were seen in the benign group (p=0.005) compared to the malignant group. Although there was a conspicuous increase in TNFα in both the groups, the increase in malignant OC was highly significant (p= 0.05), which points to the ongoing inflammatory reactions in the tumor microenvironment. Conclusion: We conclude that a higher magnitude of dysregulation of iron homeostasis observed in malignant OC patients compared to benign cases may be one of the major factors that prompt persistent ROS generation and foster inflammatory processes in the tumor microenvironment that promote subsequent cancer progression and metastasis.