A new NMR-based metabolomics approach for the diagnosis of biliary tract cancer

Background & Aims

Biliary tract cancer is highly lethal at presentation, with increasing mortality worldwide. Current diagnostic measures employing multiple criteria such as imaging, cytology, and serum tumor markers are not satisfactory, and a new diagnostic tool is needed. Because bile is a cognate metabolite-rich bio-fluid in the biliary ductal system, we tested a new metabolomic approach to develop an effective diagnostic tool.

Methods

Biles were collected prospectively from patients with cancer (n=17) or benign biliary tract diseases (n=21) with percutaneous or endoscopic methods. Nuclear magnetic resonance spectra (NMR) of these biles were analyzed using orthogonal partial least square discriminant analysis (OPLS-DA).

Results

The metabolomic 2-D score plot showed good separation between cancer and benign groups. The contributing NMR signals were analyzed using a statistical TOCSY approach. The diagnostic performance assessed by leave-one-out analysis exhibited 88% sensitivity and 81% specificity, better than the conventional markers (CEA, CA19-9, and bile cytology).

Conclusion

The NMR-based metabolomics approach provides good performance in discriminating cancer and benign biliary duct diseases. The excellent predictability of the method suggests that it can, at least, augment the currently available diagnostic approaches.

Keywords: Bile, Biliary tract cancer, Metabolomics, Diagnosis

Abbreviations: NMR, nuclear magnetic resonance spectra, OPLS-DA, orthogonal partial least square discriminant analysis, STOCSY, statistical total correlation spectroscopy, CA19-9, carbohydrate antigen 19-9, CEA, carcinoembryonic antigen, PTC, percutaneous transhepatic cholangiography, ERCP, endoscopic retrograde cholangiopancreatography, PTBD, percutaneous transhepatic biliary drainage, ENBD, endoscopic nasobiliary drainage