Bile Acid Profiling for Differential Diagnosis of Hepatobiliary Cancers and Cholelitiasis

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Abstract Cholangiocarcinoma (CCA) and pancreatic ductal adenocarcinoma (PDAC) are malignant tumors that can be characterized by low patient survival rates. They have similar anatomical proximity, morphological similarity, and an overlapping immunohistochemical profile. Even with the aid of modern imaging techniques, it is challenging to differentiate PDAC from distal CCA, as no specific biomarkers have been discovered. Bile is a promising material for research due to the possibility of relatively minimally invasive collection of biomaterial as well as direct contact with the tumor. The purpose of this work is to identify the predominant bile acids for each disease, which will help with the differential diagnosis of PDAC and CCA, while using bile from patients with cholelithiasis as a nontumor control. Bile acids were isolated from the bile of patients with three selected pathologies and studied by tandem chromatography−mass spectrometry. In the bile of patients with cholelithiasis, there are found a variety of isomers of deoxycholic acid as well as an increased proportion of glycolithocholic, glycodeoxycholic, and taurodeoxycholic acids. A predominance of taurocholic acid isomers and an increase in the proportion of glycoursodeoxycholic acid in the bile of patients with CCA is observed. Glycocholic acid is the predominant bile acid in patients with PDAC. Based on the obtained data, a set of bile acids was chosen, making it possible to compile a panel of biomarkers for the differentiation of cholelithiasis, PDAC and CCA.

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