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A predictive model based on program cell death genes for prognosis and therapeutic response in early stage hepatocellular carcinoma

  • 0Department of Hepatobiliary-Pancreatic Surgery, China-Japan Union Hospital of Jilin University, Changchun, 130033, China.
Scientific Reports +

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April 22, 2025

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April 22, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

A novel programmed cell death (PCD) score predicts poor outcomes in hepatocellular carcinoma (HCC) patients post-surgery. This PCD signature also indicates resistance to chemotherapy and immunotherapy, offering new therapeutic targets.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genomics

Background

  • Hepatocellular carcinoma (HCC) treatment often fails due to post-surgery progression and drug resistance.
  • Predictive models for HCC progression and drug response after surgery are lacking.
  • Programmed cell death (PCD) patterns are crucial in tumor development and may serve as prognostic/sensitivity indicators.

Purpose Of The Study

  • To develop a comprehensive predictive model for post-surgery HCC progression and drug response.
  • To investigate the role of diverse programmed cell death (PCD) patterns in HCC.
  • To identify potential therapeutic strategies targeting PCD in HCC.

Main Methods

  • Integrated analysis of multi-omics data (TCGA-HCC, ICGC) and clinical data from HCC patients.
  • Calculation of a novel PCD score using a four-gene signature derived from Cox regression.
  • Development of a nomogram integrating PCD signature with clinical characteristics for predictive accuracy.

Main Results

  • High PCD scores correlated with poorer prognoses in post-surgery HCC patients.
  • Two distinct HCC molecular subtypes with unique biological processes were identified via unsupervised clustering.
  • Elevated PCD levels were associated with resistance to chemotherapy and immune checkpoint inhibitors.

Conclusions

  • A novel PCD scoring system provides valuable insights into HCC prognosis and drug responsiveness.
  • The study establishes a link between PCD, immune checkpoints, and the tumor microenvironment.
  • Early-stage HCC patients might benefit from PCD-directed immune therapies.