Bile acids (BAs) are currently considered as causative agents for Cholangiocarcinoma (CCA). However, the profile of circulating BAs in CCA have not been well characterized. The aim of this study was to describe the alterations of BAs metabolism in patients with CCA compared to benign biliary diseases (BBD) and healthy controls (HC), and to discover the specific BAs as biomarkers for CCA diagnosis. The concentrations of 15 BAs in plasma were measured in a total of 329 subjects, including patients with BBD, CCA, gallbladder cancer (GC), hepatocellular carcinoma (HCC), and healthy subjects, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Binary logistic regression analysis was used to build a diagnostic model for CCA. An imbalance in the ratio of conjugated to unconjugated BAs was observed in CCA patients compared to BBD and HC groups, with higher conjugated BAs and lower unconjugated BAs. A panel of 2 BA metabolites consisting of CDCA and TCDCA showed high diagnostic performance for CCA versus BBD and CCA versus HC, with higher AUC, sensitivity and specificity than carbohydrate antigen 19−9 (CA 199), clinically employed CCA biomarker. Importantly, HCC and GC samples were also included to confirm specificity of the BA biomarkers for CCA diagnosis. In summary, specific changes in plasma concentrations of BAs may serve as diagnostic biomarkers for distinguishing CCA from BBD and HC, with higher performance than CA199.

胆汁酸（BAs）目前被认为是胆管癌（CCA）的病原体。但是，CCA中循环BA的特征尚未得到很好的表征。这项研究的目的是描述与良性胆道疾病（BBD）和健康对照（HC）相比，CCA患者中BAs代谢的变化，并发现特定的BAs作为CCA诊断的生物标志物。使用超高效液相色谱-串联质谱法对329名受试者（包括BBD，CCA，胆囊癌（GC），肝细胞癌（HCC）和健康受试者）的血浆中15种BA的浓度进行了测量（ UPLC-MS / MS）。二元逻辑回归分析用于建立CCA的诊断模型。与BBD和HC组相比，在CCA患者中观察到缀合与未缀合BA比例的失衡，其中缀合BAs较高而未缀合BAs较低。由CDCA和TCDCA组成的2种BA代谢物组显示出对CCA相对于BBD和CCA相对于HC的高诊断性能，比临床上使用的CCA生物标志物碳水化合物抗原19-9（CA 199）具有更高的AUC，敏感性和特异性。重要的是，还包括HCC和GC样品以确认BA生物标志物对CCA诊断的特异性。总而言之，BAs血浆浓度的特定变化可以作为诊断生物标志物，以区分CCA与BBD和HC，其性能要高于CA199。由CDCA和TCDCA组成的2种BA代谢物组显示出对CCA相对于BBD和CCA相对于HC的高诊断性能，比临床上使用的CCA生物标志物碳水化合物抗原19-9（CA 199）具有更高的AUC，敏感性和特异性。重要的是，还包括HCC和GC样品以确认BA生物标志物对CCA诊断的特异性。总而言之，BAs血浆浓度的特定变化可以作为诊断生物标志物，以区分CCA与BBD和HC，其性能要高于CA199。由CDCA和TCDCA组成的2种BA代谢物组显示出对CCA相对于BBD和CCA相对于HC的高诊断性能，比临床上使用的CCA生物标志物碳水化合物抗原19-9（CA 199）具有更高的AUC，敏感性和特异性。重要的是，还包括HCC和GC样品以确认BA生物标志物对CCA诊断的特异性。总而言之，BAs血浆浓度的特定变化可以作为诊断生物标志物，以区分CCA与BBD和HC，其性能要高于CA199。