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Updated: May 22, 2025

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Spatial immune scoring system predicts hepatocellular carcinoma recurrence.

Gengjie Jia1,2,3,4, Peiqi He1,2,3, Tianli Dai1,2,3

  • 1Department of Hepatobiliary Surgery, State Key Laboratory of Immune Response and Immunotherapy, Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, The First Affiliated Hospital of University of Science and Technology of China (USTC), University of Science and Technology of China, Hefei, China.

Nature
|March 13, 2025
PubMed
Summary

A new Tumor Immune Microenvironment Spatial (TIMES) score predicts hepatocellular carcinoma (HCC) recurrence risk. This score, based on spatial biomarker patterns, outperforms current systems and aids in early-stage HCC treatment decisions.

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Area of Science:

  • Oncology
  • Immunology
  • Biomarker Discovery

Background:

  • Hepatocellular carcinoma (HCC) exhibits high post-resection recurrence rates, necessitating improved risk stratification.
  • Accurate prediction of recurrence is crucial for optimizing patient outcomes and healthcare resource allocation.

Purpose of the Study:

  • To develop and validate a novel tool for predicting HCC recurrence risk post-surgery.
  • To identify spatial patterns of immune cells and biomarkers associated with HCC recurrence.

Main Methods:

  • Analysis of spatial distribution of natural killer (NK) cells and five biomarkers (SPON2, ZFP36L2, ZFP36, VIM, HLA-DRB1) in 61 HCC patients.
  • Development of the Tumor Immune Microenvironment Spatial (TIMES) score using extreme gradient boosting and inverse-variance weighting.
  • Validation of the TIMES score in a separate cohort of 231 patients across five centers.

Main Results:

  • The TIMES score demonstrated significant predictive power for HCC recurrence (hazard ratio = 88.2, P < 0.001), outperforming TNM and BCLC staging systems.
  • The validated model achieved 82.2% accuracy and 85.7% specificity in predicting recurrence.
  • Biomarker predictive value was dependent on spatial distribution, not individual expression levels alone.
  • In vivo studies showed SPON2 enhances NK cell infiltration and IFNγ secretion.

Conclusions:

  • The TIMES score is a robust, publicly accessible tool for predicting HCC recurrence risk.
  • Spatial biomarker analysis offers a novel approach to understanding and predicting tumor behavior.
  • TIMES has the potential to inform treatment decisions for early-stage HCC patients.