<p>Characterization of the urinary metabolic profile of cholangiocarcinoma in a United Kingdom population</p>

Abstract

Background: Outside South-East Asia, most cases of cholangiocarcinoma (CCA) have an obscure etiology. 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 CCA and investigate whether there were characteristic differences from those in patients with hepatocellular carcinoma (HCC), metastatic secondary liver cancer, pancreatic cancer and ovarian cancer (OCA). Methods: Spot urine specimens were obtained from 211 subjects in seven participating centers 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 (HCC, pancreatic cancer, OCA and metastatic cancer in the liver). The spectral metabolite profiles were generated using a UPLC-MS detector and data were analyzed 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 CCA 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 tumors were distinguishable from patients with hepatocellular and ovarian tumors, but no difference was observed between CCA cases and patients with pancreatic cancer or hepatic secondary metastases. Conclusion: CCA causes subtle but detectable changes in the urine metabolic profiles. The findings point toward potential applications of metabonomics in early tumor detection. However, it is key to utilize both global and targeted metabonomics in a larger cohort for in-depth characterization of the urine metabolome in hepato-pancreato-biliary disease.

Liquid Biopsies in Hepatocellular Carcinoma: Are We Winning?

“…Recently, a urinary metabolic signature was proposed to associate with CCA. This signature was capable of distinguishing CCA among other cancer entities including hepatobiliary cancers [55]. It was also recently shown that in the serum, specific metabolites might also embody novel biomarkers to distinguish intrahepatic CCA from HCC, with an AUC of 0.89, 75% sensitivity, and 90% specificity, underlining the power of metabolomic biomarkers in biliary cancer per se [56].…”

Mapping of Population Disparities in the Cholangiocarcinoma Urinary Metabolome

“…These data have previously been included in a larger study characterising the CCA profile of a UK population. [13] ! 6…”

Mapping of Population Disparities in the Cholangiocarcinoma Urinary Metabolome

“…[13] Reverse phase (RP)-UPLC-MS was performed with electrospray ionisation (ESI) in both positive and negative modes. [13] The conditions were optimized using quality control (QC) samples in terms of peak shape, reproducibility and retention time. [13] Tandem mass spectrometry Tandem mass spectrometry (MS/MS) analysis was performed using a quadrupole time-of-flight (TOF) Premier instrument (Waters MS Technologies, Manchester, UK).…”

“…[13] The conditions were optimized using quality control (QC) samples in terms of peak shape, reproducibility and retention time. [13] Tandem mass spectrometry Tandem mass spectrometry (MS/MS) analysis was performed using a quadrupole time-of-flight (TOF) Premier instrument (Waters MS Technologies, Manchester, UK). [13] Collision-induced dissociation (CID) experiments of the QC sample were performed for structural elucidation of detected ions in each ionisation mode.…”

“…[13] Tandem mass spectrometry Tandem mass spectrometry (MS/MS) analysis was performed using a quadrupole time-of-flight (TOF) Premier instrument (Waters MS Technologies, Manchester, UK). [13] Collision-induced dissociation (CID) experiments of the QC sample were performed for structural elucidation of detected ions in each ionisation mode. [13] This was conducted subsequent to the original profiling run to save time and limit analytical variations in retention time and performance that can occur when returning to the instrument for CID analysis.…”