title: Identification of bile biomarkers of biliary tract cancer through a liquid chromatography/mass spectrometry-based metabolomic method.
abstract: The incidence and mortality rate of biliary tract cancer have been increasing worldwide; however, its diagnosis and prognosis have not improved in recent years. A novel approach, termed 'metabolomics', may have the potential to be developed as an effective diagnostic tool. The present study prospectively obtained bile samples from 115 individuals, including 32 patients with biliary tract cancer, 61 patients with benign biliary tract diseases and 22 normal controls. A liquid chromatography/mass spectrometry (LC/MS)‑based approach was used to investigate the differences in bile samples between the three groups, followed by multivariate statistical analysis, which included partial least squares projection to latent structures with discriminant analysis (PLS‑DA) and orthogonal projection to latent structures with discriminant analysis (OPLS‑DA). The metabolomic 2D score plot and 3D plot revealed clear separation between the cancer, benign and normal control groups by PLS‑DA. To further address the significant difficulties in clinically differentiating between biliary tract cancer and benign biliary tract diseases, OPLS‑DA was performed to distinguish between the two disease groups and to select potential biomarkers. The cancer and benign groups were well differentiated. The metabolic analysis revealed significantly lower levels of lysophosphatidylcholine, phenylalanine, 2‑octenoylcarnitine, tryptophan and significantly higher levels of taurine‑ and glycine‑conjugated bile acids in the bile from patients with biliary tract cancer compared with those in the bile from patients with benign biliary tract disease. The present study suggested that an LC/MS‑based metabolomic investigation provides a potent and promising approach for discriminating biliary tract cancer from benign biliary tract diseases and the identified specific metabolites may offer potential as novel biomarkers for the early detection of biliary tract cancer.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Xu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Shaobing
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Ding
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Lv
authors.affiliation: Collaborative Innovation Center of Diagnosis and Treatment of Infectious Diseases, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Deying
authors.initials: D
authors.lastname: Chen
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, P.R. China.
authors.forename: Shusen
authors.initials: S
authors.lastname: Zheng
mesh_terms: D000328:Adult; D000368:Aged; D001646:Bile / Q000378:metabolism*; D001661:Biliary Tract Neoplasms / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009367:Neoplasm Staging
chemical_list: D015415:Biomarkers