Characterisation of the urinary metabolic profile of liver fluke-associated cholangiocarcinoma

Abstract

Background Human infection with Opisthorchis viverrini, a carcinogenic liver fluke inhabiting the biliary tree, is endemic in South-East Asia. Chronic infection is associated with a fatal complication, cholangiocarcinoma, a late-presenting and aggressive malignancy. Currently, annual mortality rates from cholangiocarcinoma mirror trends in incidence, due in part to limited availability of efficient prognostic and early diagnostic biomarkers. With ability to detect thousands of urinary metabolites using metabonomics, the urine metabolome holds great potential in providing an insight into system-level alterations in carcinogenesis and in identifying metabolic markers altered in response to disturbed homeostasis. Methods Global molecular profiling using reversed-phase ultra-performance liquid-chomatography mass spectrometry (RP-UPLC-MS) was utilised to acquire the urinary spectral profile of 137 Thai subjects (48 at high risk of infection, 41 with O. viverrini infection, 34 periportal fibrosis and 14 cholangiocarcinoma) from Khon Kaen, Thailand. Results Multivariate statistical analysis identified perturbation in several molecular classes related to purine metabolism and lipid metabolism in the cholangiocarcinoma urine metabolome. These markers mainly reflect changes in energy metabolism to support proliferation (increased fatty acid oxidation and purine recycling), DNA methylation and hepatic injury. Conclusions Several metabolites of biological interest were discovered from this proof-of-principle dataset. Augmenting these findings is essential to accelerate the development of urinary metabolic markers in cholangiocarcinoma.