Journal of Clinical and Translational Hepatology

Journal of Clinical and Translational Hepatology

Thursday, 12 / 09 / 2021

Articles

Abstract

ORIGINAL ARTICLE

Serum N-terminal DDR1: A Novel Diagnostic Marker of Liver Fibrosis Severity

Yuxin Zhang1,2,#, Yujie Zhang3,#, Huifang Liang1,2,#, Zeng Zhuo4, Pan Fan5, Yifa Chen1,2, Zhanguo Zhang1,2,* and Wanguang Zhang1,2,*

1  Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
2  Hubei Key Laboratory of Hepato-Biliary-Pancreatic Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
3  Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
4  Department of Gastrointestinal Surgery & Department of Gastric and Colorectal Surgical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China
5  Department of Surgery, University of Hong Kong-Shenzhen Hospital, Shenzhen, Guangdong, China
#These authors contributed equally to this work.
*Correspondence to:Zhanguo Zhang and Wanguang Zhang, Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. Tel: +86-2783665213, Fax: +86-27-83662640, E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. (ZZ) and This email address is being protected from spambots. You need JavaScript enabled to view it. (WZ)

Journal of Clinical and Translational Hepatology 2021;9(5):702-710 DOI: 10.14218/JCTH.2021.00024
Received:January 15, 2021 Accepted:April 5, 2021 Published online:April 25, 2021

Abstract

Background and Aims:The expression of discoidin domain receptor 1 (DDR1) is commonly up-regulated and undergoes collagen-induced ectodomain (N-terminal) shedding during the progression of liver fibrosis. This study aimed to evaluate the clinical utility of N-terminal DDR1 as a diagnostic biomarker for liver fibrosis.

Methods:N-terminal DDR1 shedding was evaluated using cell lines, liver fibrosis mouse models, clinical data of 298 patients collected from February 2019 to June 2020. The clinical data were divided into test and validation cohorts to evaluate the diagnostic performance of serum N-terminal DDR1.

Results:Time- and dosage-dependent N-terminal DDR1 shedding stimulated by collagen I was observed in a hepatocyte cell line model. The type I collagen deposition and serum N-terminal DDR1 levels concurrently increased in the development of liver fibrosis in mouse models. Clinical data demonstrated a significant diagnostic power of serum N-terminal DDR1 levels as an accurate biomarker of liver fibrosis and cirrhosis. The diagnostic performance was further increased when applying N-DDR1/albumin ratio, achieving area under the curve of 0.790, 0.802, 0.879, and 0.865 for detecting histological fibrosis stages F ≥2, F ≥3, F 4 with liver biopsy as a reference method, and cirrhosis according to imaging techniques, respectively. With a cut-off of 55.6, a sensitivity, specificity, positive predictive value, and negative predictive value of 82.7%,76.6%, 67.4%, and 88.3% were achieved for the detection of cirrhosis.

Conclusions:Serum N-terminal DDR1 appears to be a novel diagnostic marker for liver fibrosis.

Keywords

Liver fibrosis, Serum biomarker, DDR1, FIB-4

Journal of Clinical and Translational Hepatology 2021 vol. 9, 702-710  [ Html  ] [ PDF Full-text ]

© 2021 Authors. This is an Open Access article distributed under the terms of the  Creative Commons Attribution-Noncommercial 4.0 License(CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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