Background Biliary tract cancers (BTCs) are usually diagnosed at an advanced stage, when the disease is incurable. Currently used tumor biomarkers have limited diagnostic value for BTCs, so there is an urgent need for sensitive and specific biomarkers for their earlier diagnosis. Deregulation of the homeostasis of trace elements is involved in the carcinogenesis of different cancers, including BTCs. The objective of the study is to determine/compare the total concentrations of copper (Cu), zinc (Zn) and iron (Fe) and the proportions of free Cu and Cu bound to ceruloplasmin (Cp) and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients using inductively coupled plasma-mass spectrometry-based methods (ICP-MS). Patients and methods In this prospective, noninterventional, nonrandomized study 20 patients and 20 healthy volunteers will be enrolled to identify serum Cu, Zn and Fe levels, Cu isotopic fractionation as a predictive biomarker of response to systemic therapy of BTCs, which will be evaluated by computed tomography. Newly developed analytical methods based on ICP-MS will be applied to metal-based biomarker research in oncology. Conclusions In the study the comparison of the total concentration of selected trace elements, the proportion of free Cu and Cu bound to Cp and the isotopic ratio of 65Cu/63Cu in serum samples from healthy volunteers and cancer patients will be conducted to provide the foundation for the development of a BTC cancer screening methodology and the data on their usability as a potential predictive biomarker for BTCs of response to systemic therapy.

中文翻译：

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胆道癌患者血清样本中铜和其他微量元素的测定：前瞻性非干预性非随机临床研究方案

背景 胆道癌 (BTC) 通常在晚期才被诊断出来，此时该疾病已无法治愈。目前使用的肿瘤生物标志物对BTC的诊断价值有限，因此迫切需要敏感且特异的生物标志物对其早期诊断。微量元素稳态的失调与包括 BTC 在内的不同癌症的致癌作用有关。研究的目的是确定/比较铜 (Cu)、锌 (Zn) 和铁 (Fe) 的总浓度以及游离铜和与铜蓝蛋白 (Cp) 结合的铜的比例以及铜蓝蛋白 (Cp) 的同位素比65铜/63使用电感耦合等离子体质谱法 (ICP-MS) 检测健康志愿者和癌症患者血清样本中的铜。患者和方法 在这项前瞻性、非干预性、非随机研究中，将招募 20 名患者和 20 名健康志愿者来确定血清铜、锌和铁水平，铜同位素分馏作为 BTC 全身治疗反应的预测生物标志物，将通过以下方法进行评估： CT检查。新开发的基于ICP-MS的分析方法将应用于肿瘤学中的金属生物标志物研究。结论 研究中对所选微量元素的总浓度、游离铜和与 Cp 结合的铜的比例以及同位素比进行了比较65铜/63将检测健康志愿者和癌症患者血清样本中的铜，为开发 BTC 癌症筛查方法及其作为 BTC 对全身治疗反应的潜在预测生物标志物的可用性数据提供基础。