PMID- 33130021 OWN - NLM STAT- MEDLINE DCOM- 20210504 LR - 20210504 IS - 1879-1220 (Electronic) IS - 0960-0760 (Linking) VI - 205 DP - 2021 Jan TI - Analysis of bile acid profile in plasma to differentiate cholangiocarcinoma from benign biliary diseases and healthy controls. PG - 105775 LID - S0960-0760(20)30300-9 [pii] LID - 10.1016/j.jsbmb.2020.105775 [doi] AB - Bile acids (BAs) are currently considered as causative agents for Cholangiocarcinoma (CCA). However, the profile of circulating BAs in CCA have not been well characterized. The aim of this study was to describe the alterations of BAs metabolism in patients with CCA compared to benign biliary diseases (BBD) and healthy controls (HC), and to discover the specific BAs as biomarkers for CCA diagnosis. The concentrations of 15 BAs in plasma were measured in a total of 329 subjects, including patients with BBD, CCA, gallbladder cancer (GC), hepatocellular carcinoma (HCC), and healthy subjects, using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Binary logistic regression analysis was used to build a diagnostic model for CCA. An imbalance in the ratio of conjugated to unconjugated BAs was observed in CCA patients compared to BBD and HC groups, with higher conjugated BAs and lower unconjugated BAs. A panel of 2 BA metabolites consisting of CDCA and TCDCA showed high diagnostic performance for CCA versus BBD and CCA versus HC, with higher AUC, sensitivity and specificity than carbohydrate antigen 19-9 (CA 199), clinically employed CCA biomarker. Importantly, HCC and GC samples were also included to confirm specificity of the BA biomarkers for CCA diagnosis. In summary, specific changes in plasma concentrations of BAs may serve as diagnostic biomarkers for distinguishing CCA from BBD and HC, with higher performance than CA199. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Zhang, Xiaofen AU - Zhang X AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. FAU - Yang, Ziyao AU - Yang Z AD - Reproductive Medicine Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. FAU - Shi, Ziyu AU - Shi Z AD - Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. FAU - Zhu, Zijia AU - Zhu Z AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. FAU - Li, Cai AU - Li C AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. FAU - Du, Zhicheng AU - Du Z AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Lab of Digestive Organ Transplantation of Henan Province, Zhengzhou University, Zhengzhou 450052, China. FAU - Zhang, Yiding AU - Zhang Y AD - Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. FAU - Wang, Zipeng AU - Wang Z AD - Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China. FAU - Jiao, Zhenrui AU - Jiao Z AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. FAU - Tian, Xin AU - Tian X AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. FAU - Zhang, Ji AU - Zhang J AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. Electronic address: fcczhangj@zzu.edu.cn. FAU - Zhai, Wenlong AU - Zhai W AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Key Lab of Digestive Organ Transplantation of Henan Province, Zhengzhou University, Zhengzhou 450052, China. Electronic address: fcczhaiwl@zzu.edu.cn. FAU - Kan, Quancheng AU - Kan Q AD - Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Henan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou 450052, China. Electronic address: kanqc@zzu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20201028 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Bile Acids and Salts) SB - IM MH - Adult MH - Bile Acids and Salts/*blood MH - Bile Duct Neoplasms/blood/pathology MH - Carcinoma, Hepatocellular/*blood/pathology MH - Cholangiocarcinoma/*blood/pathology MH - Chromatography, Liquid MH - Diagnosis, Differential MH - Female MH - Humans MH - Liver Neoplasms MH - Male MH - Middle Aged MH - Neoplasms/*blood/pathology MH - Tandem Mass Spectrometry OTO - NOTNLM OT - Bile acids OT - Biomarkers OT - Cholangiocarcinoma OT - Mass spectrometry OT - Targeted metabolomics EDAT- 2020/11/02 06:00 MHDA- 2021/05/05 06:00 CRDT- 2020/11/01 20:30 PHST- 2020/07/16 00:00 [received] PHST- 2020/10/15 00:00 [revised] PHST- 2020/10/20 00:00 [accepted] PHST- 2020/11/02 06:00 [pubmed] PHST- 2021/05/05 06:00 [medline] PHST- 2020/11/01 20:30 [entrez] AID - S0960-0760(20)30300-9 [pii] AID - 10.1016/j.jsbmb.2020.105775 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2021 Jan;205:105775. doi: 10.1016/j.jsbmb.2020.105775. Epub 2020 Oct 28.