Article Abstract

Cysteinylglycine for potential diagnosis of extrahepatic cholangiocarcinoma using a novel metabolomic approach

Authors: Longjiu Cui, Xiaoqing Jiang, Liang Zhao, Yuanzhuo Chen, Zhangjun Cheng, Jiehua Li, Weifeng Tan, Alex F. Chen


Background: Currently, the diagnosis of extrahepatic cholangiocarcinoma (EHCC) is clinically difficult and remains unsatisfactory. In the present study we aimed to differentiate EHCC from benign biliary tract diseases in an effective and time-saving manner, by applying a novel metabolomic approach.
Methods: Bile was collected from patients with EHCC (n=32), primary bile duct stones (n=17) and choledochocysts (n=19), and processed for quantitative metabolomic analysis based on gas chromatographymass spectrometry (GC-MS). The data obtained from the bile samples were analyzed by using principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least square discriminant analysis. The content of cysteinylglycine in bile collected from different patients was verified using ultra-performance liquid chromatography/triple quadrupole tandem mass spectrometry. In patients with EHCC, the specificity and sensitivity of well-known tumor markers cysteinylglycine, carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA)—alone or in combination—was calculated and compared.
Results: The content of cysteinylglycine in bile of patients with EHCC was significantly lower than that in bile of patients with primary bile duct stones and choledochal cysts (P<0.01). The sensitivity and specificity of cysteinylglycine content as a diagnostic value for EHCC was 91.7% and 84.4%, respectively. Moreover, the sensitivity and specificity rates for CA19-9 were 75% and 86.1%, CEA 12.5% and 100%, and the combination of cysteinylglycine and CA19-9, 84.4% and 88.9%, respectively.
Conclusions: Cysteinylglycine can be used as a novel potential biomarker to differentiate EHCC from primary bile duct stones and choledochal cysts.