Serum trace elements and expression of antioxidant-related genes in the detection of women with ER-positive breast cancer

BACKGROUND: Breast cancer is the most frequently diagnosed malignancy among women worldwide. Trace elements, such as selenium, play a crucial role in antioxidation and have gained interest in cancer research. This study aimed to assess the association between prediagnostic serum trace element concentrations and breast cancer risk, as well as their relationship with the expression of key antioxidant enzymes in leukocytes of ER-positive breast cancer patients. METHODOLOGY: A cross-sectional study compared breast cancer patients to cancer-free individuals. Serum samples were analyzed for zinc, selenium, and copper concentrations, while leukocytes were isolated for the quantification of antioxidant-related gene expression, including SOD1, SOD2, PRDX2, PRDX5, PRDX6, TXN, UCP2, and UCP5. The predictive diagnostic capacity of identified trace elements and genes was assessed using receiver operating characteristic (ROC) curves, and correlations between gene expression and patient prognosis were evaluated. RESULTS: Breast cancer patients had lower serum selenium and zinc levels and reduced PRDX2, PRDX5, and UCP2 mRNA expression in leukocytes, whereas TXN, UCP5, and SOD2 were upregulated. Two signatures based on potential trace elements and genes showed high predictive accuracy (AUC = 0.97 and 0.98, respectively). Moreover, upregulated genes correlated with ER-positive tumors associated with poor prognosis. CONCLUSIONS: These mRNA expression patterns and bioinformatic approaches, in combination with clinical variables and trace elements plasma levels, could give an approximation to create a signature to better understand the progression or aggressiveness of ER-positive breast cancer with a simple and cost-effective blood test.