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

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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.

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References

  1. National Cancer Institute, Pancreatic Cancer. http://www.cancer.gov/cancertopics/types/pancreatic

  2. Singh M, Maitra A (2007) Precursor lesions of pancreatic cancer. Molecular pathology and clinical implications. Pancreatology 7(1): 9–19

    Article  CAS  PubMed  Google Scholar 

  3. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ (2008) Cancer statistics, 2008. CA Cancer J Clin 58(2): 71–96

    Article  PubMed  Google Scholar 

  4. Ghaneh P, Costello E, Neoptolemos JP (2007) Biology and management of pancreatic cancer. Gut 56(8): 1134–1152

    Article  CAS  PubMed  Google Scholar 

  5. Chari ST (2007) Detecting early pancreatic cancer: problems and prospects. Semin Oncol 34(4): 284–294

    Article  CAS  PubMed  Google Scholar 

  6. Louhimo J, Alfthan H, Stenman U, Haglund C (2004) Serum HCGβ and CA 72-4 are stronger prognostic factors than CEA, CA 19-9 and CA 242 in pancreatic cancer. Oncology 66(2): 126–131

    Article  CAS  PubMed  Google Scholar 

  7. Goggins M (2007) Identifying molecular markers for the early detection of pancreatic neoplasia. Semin Oncol 34(4): 303–310

    Article  CAS  PubMed  Google Scholar 

  8. Pepe MS, Etzioni R, Feng Z, Potter JD, Thompson ML, Thornquist M, Winglet M, Yasui Y (2001) Phases of biomarker development for early detection of cancer. J Natl Cancer Inst 93(14): 1054–1061

    Article  CAS  PubMed  Google Scholar 

  9. Canto MI, Goggins M, Hruban RH, Petersen GM, Giardiello FM, Yeo C, Fishman EK, Brune K, Axilbund J, Griffin C, Ali S, Richman J, Jagannath S, Kantsevoy SV, Kalloo AN (2006) Screening for early pancreatic neoplasia in high-risk individuals: a prospective controlled study. Clin Gastroenterol Hepatol 4(6): 766–781

    Article  PubMed  Google Scholar 

  10. Lattova E, Perreault H (2003) Labelling saccharides with phenylhydrazine for electrospray and matrix-assisted laser desorption-ionization mass spectroscopy. J Chromatogr B Analyt Technol Biomed Life Sci 793(1): 167–179

    Article  CAS  PubMed  Google Scholar 

  11. Lattova E, Kapkova P, Krokhin O, Perreault H (2006) Method for investigation of oligosaccharides from glycopeptides: direct determination of glycosylation sites in proteins. Anal Chem 78(9): 2977–2984

    Article  CAS  PubMed  Google Scholar 

  12. Analytical detection limit guidance http://www.dnr.state.wi.us/org/es/science/lc/OUTREACH/-Publications/LOD%20Guidance%20Document.pdf

  13. Masyuk AI, Masyuk TV, Tietz PS, Splinter PL, LaRusso NF (2002) Intrahepatic bile ducts transport water in response to absorbed glucose. Am J Physiol Cell Physiol 283(3): C785–C791

    CAS  PubMed  Google Scholar 

  14. Gruetter R, Garwood M, Ugurbil K, Seaquist ER (1996) Observation of resolved glucose signals in 1H NMR spectra of the human brain at 4 tesla. Magn Reson Med 36(1): 1–6

    Article  CAS  PubMed  Google Scholar 

  15. Nagana Gowda GA, Ijare OB, Somashekar BS, Sharma A, Kapoor VK, Khetrapal CL (2006) Single-step analysis of individual conjugated bile acids in human bile using 1H NMR spectroscopy. Lipids 41(6): 591–603

    Article  Google Scholar 

  16. Khan SA, Cox IJ, Thillainayagam AV, Bansi DS, Thomas HC, Taylor-Robinson SD (2005) Proton and phosphorus-31 nuclear magnetic resonance spectroscopy of human bile in hepatopancreaticobiliary cancer. Eur J Gastroenterol Hepatol 17(7): 733–738

    Article  CAS  PubMed  Google Scholar 

  17. Albiin N, Smith ICP, Arnelo U, Lindberg B, Bergquist A, Dolenko B, Bryksina N, Bezabeh T (2008) Detection of cholangiocarcinoma with magnetic resonance spectroscopy of bile in patients with and without primary sclerosing cholangitis. Acta Radiol 49(8): 855–862

    Article  CAS  PubMed  Google Scholar 

  18. Ijare OB, Bezabeh T, Albiin N, Arnelo U, Bergquist A, Lindberg B, Smith ICP (2008) Absence of glycochenodeoxycholic acid (GCDCA) in human bile is an indication of cholestasis: a 1H MR study. NMR Biomed (in press)

  19. Nelson DL, Cox MM (2000) Carbohydrate biosynthesis. In: Lehninger principles of biochemistry, 3rd edn. Worth, New York, pp 743–744

  20. Gordon ER, Goresky CA, Chang TH, Perlin AS (1976) The isolation and characterization of bilirubin diglucuronide, the major bilirubin conjugate in dog and human bile. Biochem J 155(3): 477–486

    CAS  PubMed  Google Scholar 

  21. Wu TW, Zumbulyadis N, Gross S, Gohlke RS (1980) Human conjugated bilirubin-isolation, biosynthesis, and direct molecular characterization. Clin Chem 26(9): 1323–1335

    CAS  PubMed  Google Scholar 

  22. Sperker B, Werner U, Murdter TE, Tekkaya C, Fritz P, Wacke R, Adam U, Gerken M, Drewelow B, Kroemer HK (2000) Expression and function of β-glucuronidase in pancreatic cancer: potential role in drug targeting. Naunyn-Schmiedeberg’s Arch Pharmacol 362(2): 110–115

    Article  CAS  Google Scholar 

  23. Prescot AP, Collins DJ, Leach MO, Dzik-Jurasz AS (2003) Human gallbladder bile: noninvasive investigation in vivo with single-voxel 1H MR spectroscopy. Radiology 229(2): 587–592

    Article  PubMed  Google Scholar 

  24. Kunnecke B, Bruns A, von Kienlin M (2007) Non-invasive analysis of gallbladder bile composition in cynomolgus monkeys using in vivo 1H magnetic resonance spectroscopy. Biochim Biophys Acta 1771(4): 544–549

    PubMed  Google Scholar 

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Authors and Affiliations

  1. National Research Council Institute for Biodiagnostics, 435 Ellice Avenue, Winnipeg, MB, R3B 1Y6, Canada

    Tedros Bezabeh, Omkar B. Ijare & Ian C. P. Smith

  2. Division of Radiology, CLINTEC, Karolinska Institutet, Stockholm, Sweden

    Nils Albiin & Bo Lindberg

  3. Division of Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden

    Urban Arnelo

Authors
  1. Tedros Bezabeh
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  2. Omkar B. Ijare
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  3. Nils Albiin
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  4. Urban Arnelo
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  5. Bo Lindberg
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  6. Ian C. P. Smith
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Correspondence to Tedros Bezabeh.

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Bezabeh, T., Ijare, O.B., Albiin, N. et al. Detection and quantification of d-glucuronic acid in human bile using 1H NMR spectroscopy: relevance to the diagnosis of pancreatic cancer. Magn Reson Mater Phy 22, 267–275 (2009). https://doi.org/10.1007/s10334-009-0171-5

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  • DOI: https://doi.org/10.1007/s10334-009-0171-5

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