Characterisation of the Urinary Metabolic Profile of Liver Fluke-Associated Cholangiocarcinoma

Munirah Alsaleh,Paiboon Sithithaworn,Narong Khuntikeo,Watcharin Loilome,Puangrat Yongvanit,Nittaya Chamadol,Thomas Hughes,Thomas O'Connor,Ross H Andrews,Elaine Holmes,Simon D Taylor-Robinson

doi:10.1016/j.jceh.2019.06.005

Abstract

BackgroundHuman 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.MethodsGlobal 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.ResultsMultivariate 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.ConclusionsSeveral 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.

Highlights

Human infection with Opisthorchis viverrini, a carcinogenic liver fluke inhabiting the biliary tree, is endemic in Southeast Asia
We aimed to investigate CCA metabolic signatures in a Thai population that distinguish early CCA development from patients with periductal fibrosis, caused by O. viverrini infection, distinct from those with parasitic infection, but without ductal fibrosis
The control groups were collected from the cholangiocarcinoma screening and care program (CASCAP) field screening programme in endemic Northeastern region.[5]

Summary

Introduction

Human infection with Opisthorchis viverrini, a carcinogenic liver fluke inhabiting the biliary tree, is endemic in Southeast Asia. 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. 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. Augmenting these findings is essential to accelerate the development of urinary metabolic markers in CCA. ( J CLIN EXP HEPATOL 2019;9:657–675)

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