Extended Data Fig. 4: An open web-tool has been developed to facilitate clinical applications of our TIMES scoring system.

a, Home page of the web-tool at http://sun.times.ustc.edu.cn/. This web-tool allows users to upload standard pathological images for HCC recurrence risk prediction (see the webpage for a tutorial and Supplementary Video 1 for a brief introduction to the TIMES scoring system). It is designed to require minimal additional work from clinicians and is tolerant to incomplete measurement input, ensuring its applicability even in cases where certain data points may be missing (b, c). b, c, High concordances between TIMES scores computed using different numbers of tiles from each compartment (AS, IF, and TC). The scatterplots display the relationship between the original TIMES scores (X-axis), calculated using whole slide images (WSI), and the TIMES scores computed using a limited number of tiles (Y-axis) from each compartment. In b, TIMES scores were calculated using 2 tiles per compartment, while in c, 3 tiles per compartment were used. The concordance between the scores was assessed using Spearman’s rank correlation coefficient (ρ). The statistical significance of the correlation was determined using a paired two-tailed Student’s t-test, with the null hypothesis that the correlation coefficient is equal to zero. Both correlations were found to be highly significant, and P < 2.2 × 10⁻¹⁶ for Spearman correlation coefficients and for linear regression coefficients, indicating a strong agreement between the TIMES scores computed using WSI and those obtained using a limited number of tiles. These results demonstrate the robustness and stability of the TIMES scoring system, even when applied to a reduced number of tissue subregions; in other words, the TIMES score was not compromised by incomplete measurement input (see Methods). d, Tentative guide for escalation of treatment strategy (using immunotherapy as a paradigm) based on TIMES score. In a diverse cohort of HCC patients with varying risks of recurrence and potential differences in immunotherapy response, our TIMES scoring system may offer an initial guideline. Patients are stratified based on their TIMES scores: (1) Risk Stratification: Patients with TIMES scores greater than 0.5 are identified as having a high risk of recurrence. (2) Immunotherapy Consideration: Among the high-risk patients, those with TIMES scores exceeding a specific threshold are recommended for immunotherapy due to the anticipated high responsiveness. Establishing this threshold necessitates comprehensive data collection from a substantial number of immunotherapy recipients to refine prediction model training. This tentative guide aims to assist in identifying HCC patients who may benefit from immunotherapy, laying the foundation for further optimization as additional data becomes available for model enhancement.

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