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Exploring therapeutic targets for hepatocellular carcinoma through druggable genes

Chao Tang1, Shuangjing Zhu2, Zhen Ding2

  • 1Department of Gastrointestinal Surgery, Chaohu Hospital of Anhui Medical University, Hefei, China.

Medicine
|October 1, 2025
PubMed

Insights

This study identifies potential therapeutic targets for hepatocellular carcinoma (HCC) using Mendelian randomization (MR). Several genes were prioritized as novel targets for developing new HCC treatments.

Area of Science:

  • Genetics
  • Oncology
  • Bioinformatics

Background:

  • Hepatocellular carcinoma (HCC) is a major global cause of cancer mortality.
  • Mendelian randomization (MR) is a valuable tool for identifying therapeutic targets in complex diseases like HCC.

Purpose of the Study:

  • To utilize two-sample MR to investigate the causal relationships between genes and HCC risk.
  • To identify and prioritize potential therapeutic targets for HCC treatment.

Main Methods:

  • Applied two-sample Mendelian randomization (MR) to assess gene-HCC risk associations.
  • Conducted replication analyses using summary-data-based MR, Bayesian co-localization, and protein-protein interaction networks.
  • Validated cell-type-specific gene expression using single-cell RNA sequencing.

Main Results:

  • Identified multiple genes causally associated with HCC risk.
  • Prioritized 3 first-level targets (HLA-DPA1, MBTPS1, TIMP3), 2 second-level targets (TNXB, HSD17B11), and 4 tertiary targets (HLA-DPB1, PLD2, KLHL8, TGFBR1).
  • Confirmed cell-type-specific expression patterns in relevant cell types.

Conclusions:

  • This research highlights several promising therapeutic targets for HCC.
  • Provides novel insights for the development of targeted therapies against HCC.
Keywords:
Mendelian randomizationcolocalizationgenehepatocellular carcinomatherapeutic target

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