332 Copper and Hormonal Dysregulation Drive EMT In Colorectal Cancer: The Role of ExcCu:Zn Ratio and Cuproplasia-Associated Proteins

Introduction/Objective Background: Colorectal cancer (CRC) progression is driven by complex interactions between hormonal imbalance and dysregulation of transition metal metabolism. These alterations converge on epithelial–mesenchymal transition (EMT), a key mechanism promoting invasion and metastasis Methods/Case Report hormones, and EMT protein expression in CRC patients. Special attention was given to the excCu:Zn ratio, which reflects exchangeable copper relative to zinc, and to the expression of cuproplasia-associated proteins (CTR1, APP, SOD1). A subgroup of 25 patients was reassessed after one month to evaluate biomarker dynamics. Results CRC patients exhibited functional iron deficiency and increased ceruloplasmin-to-transferrin ratios. Progesterone levels inversely correlated with EMT markers in healthy mucosa. The ­excCu:Zn ratio was significantly elevated in CRC (up to 33-fold vs. controls), correlated with tumor stage, and demonstrated excellent discriminatory power (ROC AUC = 0.94). After one month, this ratio decreased by 25% in the follow-up subgroup, indicating potential responsiveness to tumor burden. Tumor tissues showed copper depletion and altered expression of CTR1, APP, and SOD1. CTR1 and SOD1 were negatively associated with fibronectin and positively with E-cadherin, suggesting an anti-EMT role. Conclusion The excCu:Zn ratio and copper-handling proteins provide integrated insight into systemic and tissue-level dysregulation in CRC. This copper-centered axis, together with hormonal imbalance, contributes to EMT modulation and may serve as a promising target for non-invasive biomarkers and therapeutic strategies