Clinical and Experimental Hepatology
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ISSN: 2392-1099
Clinical and Experimental Hepatology
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4/2025
vol. 11
 
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abstract:
Original paper

Identification of novel therapeutic targets for liver fibrosis, cirrhosis, and hepatocellular carcinoma via dual-omics analysis and preliminary exploration of regulatory mechanisms

Jian Chen
1
,
Rongge Cao
1
,
Zhiyuan He
2
,
Zifan Li
1
,
Yanan Hong
1
,
Chuanzeng Ren
1
,
Ying Wang
1
,
Jiazhao Wu
1
,
Yongqing Liu
1
,
Honghai Xia
1

  1. Department of Emergency Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
  2. Department of Allergy, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
Clin Exp HEPATOL 2025; 11, 4
DOI: https://doi.org/10.5114/ceh.2025.155448
Online publish date: 2025/12/15
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Aim
Liver fibrosis (LF), cirrhosis, and hepatocellular carcinoma (HCC) are strongly correlated and impose a heavy burden on the global healthcare system. Currently, there are no effective treatments, and thus we performed dual-omics analysis to identify new targets and regulatory mechanisms.

Material and methods
A two-sample Mendelian randomization (MR), with cis-expression quantitative trait locus (cis-eQTL) as the genomic variables and cis-protein quantitative trait locus (cis-pQTL) as the proteomic variables, was performed to identify candidate therapeutic targets for LF, cirrhosis, and HCC at the gene and protein levels. Colocalization analysis was performed to screen for significant candidate targets. Moreover, the results were validated using summary-data-based MR (SMR) analysis. To further explore the downstream regulatory mechanisms of the targets, we performed two-step MR, with circulating metabolites, immune cells, gut microbiota, and inflammatory proteins as mediating variables.

Results
Through the two-sample MR, we identified 9 candidate targets for LF, 6 targets for cirrhosis, and 12 targets for HCC. Two significant therapeutic targets for LF, 3 targets for cirrhosis, and 1 target for HCC were identified through colocalization analysis. Among them, DMWD, CDK13, ATRAID, SLC5A6, and CD300LD were validated through SMR. Further analysis revealed that ATRAID might inhibit cirrhosis by upregulating threonine levels. In contrast, CDK13 was predicted to promote LF by suppressing CD20 on naive-mature B cells.

Conclusions
In this study, dual-omics analysis identified new therapeutic targets for LF, cirrhosis, and HCC, as well as potential regulatory mechanisms; these results lay the foundation for further investigations into the disease mechanisms and new drug development.

keywords:

liver fibrosis, cirrhosis, hepatocellular carcinoma, dual-omics, targets
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