Circulating osteocyte‐related biomarkers (vitamin D, sclerostin, dickkopf-1), hepcidin, and oxidative stress markers in early breast cancer: Their impact in disease progression and outcome

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 204; p. 105773
• Main Authors: El-Mahdy, Reham I, Zakhary, Madeha M., Maximous, Doaa W., Mokhtar, Abeer A, El Dosoky, Mahmoud I.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.11.2020; Elsevier BV
• Subjects: 25-Hydroxyvitamin D; Adaptor Proteins, Signal Transducing - blood; Adult; Aged; Biomarkers; Biomarkers - blood; Breast cancer; Breast diseases; Breast Neoplasms - blood; Case-Control Studies; Dickkopf-1 (DKK1); Disease Progression; Dkk1 protein; Female; Hepcidin; Hepcidins - blood; Humans; Intercellular Signaling Peptides and Proteins - blood; Middle Aged; Osteocytes; Oxidative Stress; Prognosis; Sclerostin (SOST); SOST protein; Spectrophotometry; Tumor progression; Vitamin D; Vitamin D - blood; Vitamins - blood; Oxidative stress; PR; RANKL; EPO; FPN; MRI; OPG; BCBreast; MDA; LPER; RXRA; Tumor progression; Hb; 25(OH); SOST; Sclerostin (SOST); FGF23; BMI; No; BMP; OS; 25-hydroxyvitamin D; VDR; BOLCs; HCC; SOD; Breast cancer; DKK1; EMT; ER; GPx; IL-6; Dickkopf-1 (DKK1); CT; FZD; CRA; LRP5/6low-density; WIF; TCF; ROS; HAMP; Hepcidin; ELISA
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2020.105773

•Breast cancer is associated with altered circulating osteocyte‐related biomarkers, hepcidin, and oxidative stress parameters.•Wnt inhibitors and hepcidin are inversely correlated to vitamin D in early BC.•Vitamin D and SOD have a good predictive of outcome in early BC.•Hepcidin and iron metabolism are crucial elements in BC development via oxidative stress.•Circulating DKK1, hepcidin, and SOD differ between benign breast disease and controls. Breast cancer (BC) is a major concern to female health worldwide. We assessed the circulating osteocyte‐related biomarkers, hepcidin, and oxidative stress status among early-stage BC patients in aspects of clinical severity and impact on the outcome. The study incorporated 73 patients categorized into 57 early-stage BC and 16 benign breast diseases and 30 healthy controls. Serum 25-hydroxyvitamin D [25(OH)D], sclerostin (SOST), dickkopf-1(DKK1), and hepcidin were measured using ELISA, while, serum oxidative stress markers were assessed by spectrophotometry. Our results show that patients with BC showed significant increase in the mean levels of DKK1, SOST, hepcidin, and LPER and significant decrease in the mean levels of 25(OH)D, SOD, GPx, and Hb when compared with controls and benign breast diseases. Significantly higher DKK1, hepcidin, and SOD levels among benign breast diseases were found in comparison to control group. There were significantly lower levels of 25(OH)D, SOD, and Hb and significantly higher levels of SOST, DKK1, hepcidin, No, and LPER with advanced grade. Lower levels of 25(OH)D, SOD and higher levels of SOST, hepcidin were observed with increasing the malignant stage. Reduced levels of 25(OH)D, and SOD were significantly associated with poor prognosis and were strong predictors among BC. There were significant negative correlations between 25(OH)D with LPER, SOST, and hepicidin. We conclude that low 25(OH)D, high SOST, DKK1, and hepcidin, and dysregulated oxidative stress could be helpful in early detection and assessment of BC. 25(OH)D, and SOD were the most relevant to tumor progression and prognosis which indicate a significant role in the BC pathogenesis and could be promising targets in management. Our research paves the way to disrupt vicious circle between these biomarkers to obtain the best care of BC.