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Identification of Causal Plasma Proteins in Hepatocellular Carcinoma via Two-Sample Mendelian Randomization and Integrative Transcriptomic‒Proteomic Analysis

  • 0College of Liberal Arts and Sciences, University of Florida, Gainesville, Florida.
Cancer Research Communications +

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February 24, 2025

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February 24, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study identifies seven causal plasma proteins for hepatocellular carcinoma (HCC) using proteomic data and Mendelian randomization. These findings offer new targets for early HCC diagnosis and treatment.

Area Of Science

  • Proteomics
  • Genetics
  • Oncology

Background

  • Hepatocellular carcinoma (HCC) is a major global health concern.
  • Early detection and targeted therapies for HCC are crucial.
  • Plasma protein identification offers a promising avenue for HCC research.

Purpose Of The Study

  • To identify causal plasma proteins associated with HCC using large-scale proteomic data.
  • To explore the potential of these proteins as diagnostic and therapeutic targets for HCC.
  • To investigate the role of identified proteins in HCC oncogenesis and identify potential drug candidates.

Main Methods

  • Two-sample Mendelian randomization (MR) analysis was employed using proteomic data from the UK Biobank Pharma Proteomics Project.
  • Sensitivity, directionality, and colocalization analyses were performed to validate MR findings.
  • Single-cell RNA sequencing data and drug databases (DSigDB/DrugBank) were utilized for validation and drug discovery.

Main Results

  • Seven plasma proteins (ASS1, B2M, FUOM, GABARAPL1, ST8SIA1, STOML2, KRT8) showed potential causal associations with HCC.
  • ASS1, KRT8, and STOML2 demonstrated the strongest causal effects.
  • KRT8 was predominantly expressed in hepatic progenitor cells and implicated in HCC oncogenesis.
  • Potential drugs targeting ASS1, KRT8, and STOML2 were identified.

Conclusions

  • Novel causal plasma proteins linked to HCC were identified, advancing understanding of the disease.
  • These proteins represent potential biomarkers for early HCC diagnosis.
  • The identified drug targets offer new therapeutic strategies for hepatocellular carcinoma.