Diagnostic role of biliary pancreatic elastase for cholangiocarcinoma in patients with cholestasis

Chiung Yu Chen, Wei Lun Tsai, Hui Chun Wu, Mei Jywan Syu, Cheng Chung Wu, Shu Chu Shiesh

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Abstract

Background: A wide array of proteins is secreted into the bile and may be associated with biliary tract diseases. We attempted to discover novel biomarker in bile for cholangiocarcinoma. Methods: Bile was collected from patients with bile duct obstruction. Proteins were separated by 2-dimensional electrophoresis and identified by mass spectrometry. Levels of mRNA and protein expression of the candidate biomarker were analyzed by real-time PCR and Western blotting, respectively, whereas enzyme activity was measured by a kinetic method. The diagnostic efficacy was assessed by receiver operating characteristic (ROC) curve analysis. Results: Pancreatic elastase (PE) 3B was identified as a biomarker for cholangiocarcinoma. The mRNA of PE 3B was up-regulated in cancerous tissues, compared to non-cancerous tissues. The protein expression and enzyme activity of PE in bile were increased in patients with cholangiocarcinoma, compared to gallstone patients. Biliary amylase activity was used to correct the presence of pancreaticobiliary reflux. Significantly higher PE/amylase ratios in bile were found in patients with cholangiocarcinoma (0.214 ± 0.045) than those with gallstone (0.023 ± 0.005, p < 0.001). The area under the ROC curve of the ratio was 0.877 (95% CI: 0.765 to 0.988). Using 0.065 as a cutoff value, the ratio distinguished malignant from benign causes of biliary obstruction with a sensitivity of 82% and a specificity of 89%. Conclusion: PE in bile is a biomarker for cholangiocarcinoma and the combination measurement of PE and amylase enhances diagnostic efficacy.

Original languageEnglish
Pages (from-to)82-89
Number of pages8
JournalClinica Chimica Acta
Volume390
Issue number1-2
DOIs
Publication statusPublished - 2008 Apr 1

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical

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