2. Academic Validation
  3. Discovery of glycocholic acid and taurochenodeoxycholic acid as phenotypic biomarkers in cholangiocarcinoma

Discovery of glycocholic acid and taurochenodeoxycholic acid as phenotypic biomarkers in cholangiocarcinoma

  • Sci Rep. 2018 Jul 23;8(1):11088. doi: 10.1038/s41598-018-29445-z.
Won-Suk Song 1,  Hae-Min Park 2,  Jung Min Ha 3,  Sung Gyu Shin 4,  Han-Gyu Park 4,  Joonwon Kim 1,  Tianzi Zhang 5,  Da-Hee Ahn 4,  Sung-Min Kim 4,  Yung-Hun Yang 6,  Jae Hyun Jeong 4,  Ashleigh B Theberge 5,  Byung-Gee Kim 1,  Jong Kyun Lee 7,  Yun-Gon Kim 8
Affiliations

Affiliations

  • 1 School of Chemical and Biological Engineering, Seoul National University, Seoul, 08826, Korea.
  • 2 Departments of Chemistry and Molecular Biosciences, Northwestern University, Evanston, Illinois, 60208, United States.
  • 3 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, 0635, Korea.
  • 4 Department of Chemical Engineering, Soongsil University, Seoul, 06978, Korea.
  • 5 Department of Chemistry, University of Washington, Box 351700, Seattle, WA, 98195, United States.
  • 6 Department of Biological Engineering, Konkuk University, Seoul, 05029, Korea.
  • 7 Division of Gastroenterology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, 0635, Korea. [email protected].
  • 8 Department of Chemical Engineering, Soongsil University, Seoul, 06978, Korea. [email protected].
PMID: 30038332 DOI: 10.1038/s41598-018-29445-z
Abstract

Although several biomarkers can be used to distinguish cholangiocarcinoma (CCA) from healthy controls, differentiating the disease from benign biliary disease (BBD) or pancreatic Cancer (PC) is a challenge. CCA biomarkers are associated with low specificity or have not been validated in relation to the biological effects of CCA. In this study, we quantitatively analyzed 15 biliary bile acids in CCA (n = 30), BBD (n = 57) and PC (n = 17) patients and discovered glycocholic acid (GCA) and taurochenodeoxycholic acid (TCDCA) as specific CCA biomarkers. Firstly, we showed that the average concentration of total biliary bile acids in CCA patients was quantitatively less than in Other patient groups. In addition, the average composition ratio of primary bile acids and conjugated bile acids in CCA patients was the highest in all patient groups. The average composition ratio of GCA (35.6%) in CCA patients was significantly higher than in Other patient groups. Conversely, the average composition ratio of TCDCA (13.8%) in CCA patients was significantly lower in all patient groups. To verify the biological effects of GCA and TCDCA, we analyzed the gene expression of bile acid receptors associated with the development of CCA in a CCA cell line. The gene expression of transmembrane G protein coupled receptor (TGR5) and sphingosine 1-phosphate receptor 2 (S1PR2) in CCA cells treated with GCA was 8.6-fold and 3.4-fold higher compared with control (untreated with bile acids), respectively. Gene expression of TGR5 and S1PR2 in TCDCA-treated cells was not significantly different from the control. Taken together, our study identified GCA and TCDCA as phenotype-specific biomarkers for CCA.

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