Spatial immune scoring system predicts hepatocellular carcinoma recurrence.

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.