Detection and quantification of d-glucuronic acid in human bile using 1H NMR spectroscopy: relevance to the diagnosis of pancreatic cancer

Tedros Bezabeh, Omkar B. Ijare, Nils Albiin, Urban Arnelo, Bo Lindberg and Ian C. P. Smith

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Abstract

Objective  

There are no specific biomarkers available for the definitive diagnosis of pancreatic cancer. Analysis of d-glucuronic acid (GlcUA) in bile could be valuable in this regard.

Materials and methods  

Bile samples obtained from patients with pancreatic cancer (n = 4), chronic pancreatitis (n = 3) and control patients with biliary obstruction (n = 10) were analyzed by 1H NMR spectroscopy. GlcUA was quantified from the peak area of the α-1CH signal (at 5.24 ppm) obtained by deconvolution.

Results  

GlcUA was detected in human bile by one-dimensional 1H NMR and two-dimensional 1H–1H COSY and TOCSY experiments. Quantification of GlcUA was achieved by measuring the peak area of the α-1CH signal using CPMG experiment, and the quantities of GlcUA were calibrated to account for the attenuation due to T 2 relaxation. GlcUA was observed at elevated levels in bile samples obtained from pancreatic cancer patients, whereas it was either absent or found in negligible amounts in control and chronic pancreatitis patients. The reason for the presence of elevated levels of GlcUA could be the hydrolysis of biliary bilirubin diglucuronide by β-glucuronidase, released excessively from pancreatic tissue during the course of malignancy.

Conclusion  

Analysis of d-glucuronic acid in bile could be valuable in the detection of pancreatic cancer, and detecting GlcUA by in vivo 1H MRS has the potential to help in the non-invasive diagnosis of pancreatic cancer. Given that only four cancer patients have been studied so far, the new biomarker is regarded as a preliminary finding, but one that warrants further investigation.

Keywords   d-Glucuronic acid - Glucuronidase activity - Human bile - Magnetic resonance spectroscopy - Pancreatic cancer - Pancreatitis

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