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<p>The development of the immune system (ISD) plays a pivotal role in both the genesis and progression of tumors, yet its specific functions in hepatocellular carcinoma (HCC) and the mechanisms behind sorafenib resistance remain elusive. In our investigation, we initially created 167 algorithms by amalgamating 10 distinct machine learning algorithms to identify an optimal and potent ISD-related signature (ISDRS), which proved to be superior to 73 previously published signatures. Moreover, we found that resistance to sorafenib was associated with both ISD levels and ISDRS. These, in turn, exhibited a positive correlation with the infiltration of T regulatory cells (Tregs) and a negative correlation with the levels of IL-6/IL-6R. Furthermore, through single-cell analysis, we uncovered a novel Tregs subgroup that contributes to sorafenib resistance and identified BATF as a potential biomarker for this subgroup.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年9月30日

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  • Shiji Wu,
  • Xingte Chen,
  • Huipeng Fang,
  • Yaqi Zhong,
  • Qizhen Huang,
  • Liang Hong,
  • Lingdong Shao,
  • Lei Wang,
  • Junxin Wu

摘要

The development of the immune system (ISD) plays a pivotal role in both the genesis and progression of tumors, yet its specific functions in hepatocellular carcinoma (HCC) and the mechanisms behind sorafenib resistance remain elusive. In our investigation, we initially created 167 algorithms by amalgamating 10 distinct machine learning algorithms to identify an optimal and potent ISD-related signature (ISDRS), which proved to be superior to 73 previously published signatures. Moreover, we found that resistance to sorafenib was associated with both ISD levels and ISDRS. These, in turn, exhibited a positive correlation with the infiltration of T regulatory cells (Tregs) and a negative correlation with the levels of IL-6/IL-6R. Furthermore, through single-cell analysis, we uncovered a novel Tregs subgroup that contributes to sorafenib resistance and identified BATF as a potential biomarker for this subgroup.