Demarcating the Development of Cirrhosis and Its Complications via Plasma Proteomic Features in an Asymptomatic Population.

Journal: Journal of proteome research
Published Date: Jun 18, 2025

Abstract

The early detection of liver cirrhosis and its complications is a conundrum in clinical practice. We aim to address this conundrum using proteomic features of plasma. A total of 52,891 participants without cirrhosis or its complications were recruited from the UK Biobank longitudinal population cohort. We identified GDF15, CDCP1, ADGRG1, GGT1, HGF, MFAP4, and THBS2 from 2923 plasma proteins and developed proteomic models to predict early cirrhosis and its complications occurring at 5, 10, and over 10 years. These protein markers were validated to be associated with liver fibrosis in an external liver biopsy cohort. High levels of GDF15 and GGT1 were associated with an increased risk of developing cirrhosis and its complications. The two proteins began to change at least 13 years before the diagnosis of cirrhosis and its complications. Transcriptomic analysis delineated the cellular localization of these proteins in the liver and demonstrated their expression changes during fibrosis progression across different etiologies. Mendelian randomization analyses further supported a potential causal effect of GGT1 on cirrhosis.

Authors

  • Zhuoshuai Liang
    Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China.
  • Zhirong Li
    School of Architecture and Art, Central South University, Changsha, 410083, China.
  • Huizhen Jin
    Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China.
  • Wenhui Gao
    Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China.
  • Ruofei Li
    Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China.
  • Xinmeng Hu
    Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China.
  • Zhantong Liu
    Department of Epidemiology and Biostatistics, School of Public Health of Jilin University, Changchun 130021, China.
  • Xiaoyang Li
    Department of Thoracic Surgery, West China Hospital of Sichuan University, Chengdu, 610041, China.
  • Yi Cheng
    College of Engineering, Lishui University, Lishui, 323000, China.
  • Lingfei Guo
    Key Laboratory of Endocrine Glucose & Lipids Metabolism and Brain Aging, Ministry of Education, Department of Radiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
  • Yawen Liu
    School of Biological Science and Medical Engineering, Beihang University, Beijing, China.

Keywords

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