Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2021; 27(17): 1973-1992
Published online May 7, 2021. doi: 10.3748/wjg.v27.i17.1973
S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis
Xi-Hua Dong, Di Dai, Zhi-Dong Yang, Xiao-Ou Yu, Hua Li, Hui Kang
Xi-Hua Dong, Di Dai, Zhi-Dong Yang, Xiao-Ou Yu, Hua Li, Hui Kang, Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Author contributions: All authors participated in the design, interpretation of the studies, analysis of the data and review of the manuscript; Dong XH wrote the manuscript; Dong XH, Dai D and Yang ZD conducted the experiment; Yu XO and Li H collected data; Dong XH, Yu XO and Li H analyzed the data; the article was approved by Kang H; The final version of the article was approved by all authors.
Supported by National Natural Science Foundation of China, No. 81871723.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of China Medical University (Approval No. 2018-89-2).
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals [China Medical University Application for Laboratory Animal Welfare and Ethical review (201702 Edition)].
Conflict-of-interest statement: The authors declare that there are no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Hui Kang, PhD, Professor, Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Shenyang 110001, Liaoning Province, China. kanghui65@sina.com
Received: December 7, 2020
Peer-review started: December 7, 2020
First decision: January 10, 2021
Revised: January 23, 2021
Accepted: March 10, 2021
Article in press: March 10, 2021
Published online: May 7, 2021
ARTICLE HIGHLIGHTS
Research background

Primary biliary cholangitis (PBC) is an autoimmune liver disease that mostly affects women. Fatigue and persistent pruritus are the most obvious symptoms. PBC may lead to cholestasis, liver fibrosis, cirrhosis and, eventually, liver failure. The injury mechanism of intrahepatic biliary epithelial cells is the key to investigating the pathogenesis of PBC, but the accurate relationship between cholestasis and liver fibrosis is still indistinct.

Research motivation

To explore the target genes of intrahepatic biliary epithelial cell injury in PBC. To search for plasma biomarkers for early diagnosis and staging of PBC. To lay a foundation for further study on the pathogenesis of PBC.

Research objectives

To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6 (S100A6) messenger ribonucleic acid (mRNA), LINC00312, LINC00472, and LINC01257 in primary biliary cholangitis.

Research methods

The up-regulation of S100A6 was identified by double immunofluorescence in a bile duct ligation mouse model. We used quantitative reverse transcription-polymerase chain reaction to analyze the relative expression levels of S100A6 mRNA, long noncoding ribonucleic acids (lncRNAs) LINC00312, LINC00472 and LINC01257 both in patients with PBC and in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate.

Research results

The relative expression levels of S100A6 mRNA, LINC00472 and LINC01257 were up-regulated while LINC00312 was down-regulated in both the plasma of patients with PBC and in human intrahepatic biliary epithelial cells treated with glyco-chenodeoxycholate.

Research conclusions

These four genes may potentially act as novel biomarkers for the diagnosis of PBC. Moreover, LINC00472 acts as a biomarker for staging in PBC.

Research perspectives

Although we have demonstrated that S100A6 and related lncRNAs may be biomarkers for the diagnosis and staging of PBC, their detailed value needs to be analyzed in a large sample. The specific mechanisms of S100A6 and lncRNAs require further investigation.