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循环成骨细胞相关生物标志物(维生素 D、骨硬化蛋白、Dickkopf-1)、铁调素和氧化应激标志物在早期乳腺癌中的作用:对疾病进展和结局的影响。

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.

机构信息

Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Assiut University, Egypt.

Department of Medical Biochemistry & Molecular Biology, Faculty of Medicine, Assiut University, Egypt.

出版信息

J Steroid Biochem Mol Biol. 2020 Nov;204:105773. doi: 10.1016/j.jsbmb.2020.105773. Epub 2020 Oct 13.

DOI:10.1016/j.jsbmb.2020.105773
PMID:33065276
Abstract

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.

摘要

乳腺癌(BC)是全球女性健康的主要关注点。我们评估了早期 BC 患者的循环破骨细胞相关生物标志物、铁调素和氧化应激状态,从临床严重程度和对结局的影响方面进行评估。该研究纳入了 73 名患者,分为 57 名早期 BC 患者、16 名良性乳腺疾病患者和 30 名健康对照组。采用 ELISA 法检测血清 25-羟维生素 D [25(OH)D]、骨硬化蛋白(SOST)、Dickkopf-1(DKK1)和铁调素,采用分光光度法检测血清氧化应激标志物。我们的研究结果显示,与对照组和良性乳腺疾病组相比,BC 患者的 DKK1、SOST、铁调素和 LPER 的平均水平显著升高,25(OH)D、SOD、GPx 和 Hb 的平均水平显著降低。与对照组相比,良性乳腺疾病患者的 DKK1、铁调素和 SOD 水平显著升高。随着疾病分级的升高,25(OH)D、SOD 和 Hb 的水平显著降低,SOST、DKK1、铁调素、NO 和 LPER 的水平显著升高。随着恶性程度的增加,25(OH)D、SOD 的水平降低,SOST、铁调素的水平升高。25(OH)D 和 SOD 水平降低与预后不良显著相关,是 BC 的强预测因子。25(OH)D 与 LPER、SOST 和铁调素呈显著负相关。我们的结论是,低 25(OH)D、高 SOST、DKK1 和铁调素以及氧化应激失调有助于早期发现和评估 BC。25(OH)D 和 SOD 与肿瘤进展和预后最相关,表明其在 BC 发病机制中具有重要作用,可能成为治疗的有前景的靶点。我们的研究为打破这些生物标志物之间的恶性循环以获得 BC 的最佳治疗铺平了道路。

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