Background Outside South-East Asia, most cases of cholangiocarcinoma have an obscure aetiology. There is often diagnostic uncertainty. Metabolomics using ultraperformance liquid chromatography mass spectrometry (UPLC-MS) offers the portent to distinguish disease-specific metabolic signatures. We aimed to define such a urinary metabolic signature in a patient cohort with sporadic cholangiocarcinoma and investigate whether there were characteristic differences from those in patients with hepatocellular carcinoma, metastatic secondary liver cancer, pancreatic and ovarian cancer.

Methods Spot urine specimens were obtained from 211 subjects in seven participating centres across the UK. Samples were collected from healthy controls and from patients with benign hepatic disease (gallstone, biliary strictures, sphincter of Oddi dysfunction and viral hepatitis) and patients with malignant conditions (hepatocellular carcinoma, pancreatic cancer, ovarian cancer and metastatic cancer in the liver). The spectral metabolite profiles were generated using a UPLC-MS detector and data were analysed using multivariate and univariate statistical analyses.

Results The greatest class differences were seen between the metabolic profiles of disease-free controls compared to individuals with cholangiocarcinoma with altered acylcarnitine, bile acid and purine levels. Individuals with benign strictures showed comparable urine profiles to patients with malignant bile duct lesions. The metabolic signatures of patients with bile duct tumours were distinguishable from patients with hepatocellular and ovarian tumours, but no difference was observed between CCA cases and patients with pancreatic cancer or hepatic secondary metastases.

Conclusion Cholangiocarcinoma causes subtle but detectable changes in the urine metabolic profiles. The findings point towards potential applications of metabonomics in early tumour detection. However, it is key to utilize both global and targeted metabonomics in a larger cohort for in-depth characterisation of the urine metabolome in hepato-pancreato-biliary disease.