JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Immune system development-related signature predicts prognosis and sorafenib-treatment resistance of hepatocellular carcinoma by intergrating machine learning and single-cell analyses

  • 0Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, 420 Fuma Rd, Jin'an District, Fuzhou, 350011, Fujian, China.
Scientific Reports +

|

September 30, 2025

|

September 30, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

This study identifies an immune system development signature (ISDRS) crucial for hepatocellular carcinoma (HCC). The ISDRS predicts sorafenib resistance, linked to regulatory T cells (Tregs) and IL-6/IL-6R levels.

Area Of Science

  • Oncology
  • Immunology
  • Bioinformatics

Background

  • The immune system's role in cancer development and progression is significant.
  • Specific immune system development (ISD) functions in hepatocellular carcinoma (HCC) and sorafenib resistance mechanisms are not well understood.

Purpose Of The Study

  • To identify a potent immune system development-related signature (ISDRS) for HCC.
  • To investigate the association between ISDRS, ISD levels, and sorafenib resistance.
  • To explore the role of regulatory T cells (Tregs) and cytokine signaling in sorafenib resistance.

Main Methods

  • Developed 167 algorithms by combining 10 machine learning algorithms to identify an optimal ISDRS.
  • Correlated ISDRS and ISD levels with sorafenib resistance, T regulatory cell (Treg) infiltration, and IL-6/IL-6R levels.
  • Utilized single-cell analysis to identify novel Tregs subgroups and potential biomarkers.

Main Results

  • The developed ISDRS outperformed 73 previously published signatures.
  • Sorafenib resistance was positively correlated with ISD levels and ISDRS.
  • Sorafenib resistance showed a positive correlation with Treg infiltration and a negative correlation with IL-6/IL-6R levels.
  • A novel Tregs subgroup contributing to sorafenib resistance was identified, with BATF as a potential biomarker.

Conclusions

  • The study established a superior ISDRS for HCC, offering insights into sorafenib resistance.
  • Tregs and IL-6/IL-6R signaling are implicated in sorafenib resistance in HCC.
  • BATF may serve as a biomarker for a specific Tregs subgroup driving sorafenib resistance.

Keywords: