Urinary Metabolic Profiling of Liver Fluke-Induced Cholangiocarcinoma-A Follow-Up Study

Background/Aims: Global liquid chromatography mass spectrometry (LC-MS) profiling in a Thai population has previously identified a urinary metabolic signature in Opisthorchis viverrini-induced cholangiocarcinoma (CCA), primarily characterised by disturbance in acylcarnitine, bile acid, steroid, and purine metabolism. However, the detection of thousands of analytes by LC-MS in a biological sample in a single experiment potentially introduces false discovery errors. To verify these observed metabolic perturbations, a second validation dataset from the same population was profiled in a similar fashion. Methods: Reverse-phase ultra-performance liquid -chromatog-raphy mass spectrometry was utilised to acquire the global spectral profile of 98 spot urine samples (from 46 healthy volunteers and 52 CCA patients) recruited from Khon Kaen, northeast Thailand (the highest incidence of CCA globally). Results: Metabolites were differentially expressed in the urinary profiles from CCA patients. High urinary elimination of bile acids was affected by the presence of obstructive jaundice. The urine metabo-lome associated with non-jaundiced CCA patients showed a distinctive pattern, similar but not identical to pub-lished studies. A panel of 10 metabolites achieved a diagnostic accuracy of 93.4% and area under the curve value of 98.8% (CI = 96.3%-100%) for the presence of CCA. Conclusions: Global characterisation of the CCA urinary metab-olome identified several metabolites of biological interest in this validation study. Analyses of the diagnostic util-ity of the discriminant metabolites showed excellent diagnostic potential. Further larger scale studies are required to confirm these findings internationally, particularly in comparison to sporadic CCA, not associated with liver fluke infestation.

Automated summary

This study used LC-MS profiling to analyze urinary metabolites in a Thai population and identified metabolic characteristics of Opisthorchis viverrini-induced cholangiocarcinoma (CCA). Utilizing a larger sample size, this study confirmed the diagnostic potential of certain metabolites.