Background: Human infection with Opisthorchis viverrini, a carcinogenic liver fluke inhabiting the biliary tree, is endemic in Southeast Asia. Chronic infection is associated with a fatal complication, cholangiocarcinoma (CCA), a late-presenting and aggressive malignancy. Currently, annual mortality rates from CCA 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 homoeostasis.
Methods: Global molecular profiling using reversed-phase ultraperformance liquid chromatography mass spectrometry 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 CCA) from Khon Kaen, Thailand.
Results: Multivariate statistical analysis identified perturbation in several molecular classes related to purine metabolism and lipid metabolism in the CCA 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 CCA.
Keywords: Opisthorchis viverrini; acetaminophen, APAP; bile duct cancer; carnitine palmitoyltransferase 1, CPT1; carnitine palmitoyltransferase 2, CPT2; carnitine/acylcarnitine translocase, CACT; cholangiocarcinoma screening and care program, CASCAP; cholangiocarcinoma, CCA; data-dependent acquisition, DDA; electrospray ionisation, ESI; hypoxanthine phosphoribosyltransferase 1, HPRT1; hypoxanthine-guanine phosphoribosyltransferase, HPRT; mass spectrometry; metabonomics; orthogonal projections to latent structures discriminant analysis, OPLS-DA; periductal fibrosis, PDF; periportal fibrosis, PPF; primary biliary cholangitis, PBC; primary sclerosing cholangitis, PSC; principal component analysis, PCA; reversed-phase ultra-performance liquid-chromatography mass spectrometry, RP-UPLC-MS; ultra-performance liquid chromatography mass spectrometry, UPLC-MS; variable importance in projection, VIP.
© 2019 The Authors.