Spatial immune scoring system predicts hepatocellular carcinoma recurrence

文献类型： 外文期刊

第一作者： Jia, Gengjie

作者： Jia, Gengjie;He, Peiqi;Dai, Tianli;Wang, Jiabei;Sun, Mengyuan;Li, Fuling;Liu, Yao;Lim, Tony Kiat Hon;Tao, Qingping;Wang, Wei;Umar, Ahitsham;Nashan, Bjoern;Liu, Lianxin;Sun, Cheng;Jia, Gengjie;He, Peiqi;Dai, Tianli;Sun, Mengyuan;Li, Fuling;Tao, Qingping;Wang, Wei;Umar, Ahitsham;Sun, Cheng;Jia, Gengjie;He, Peiqi;Dai, Tianli;Wang, Jiabei;Sun, Mengyuan;Li, Fuling;Liu, Yao;Tao, Qingping;Wang, Wei;Jia, Gengjie;Hao, Shuxia;Goh, Denise;Wee, Felicia;Lim, Jeffrey Chun Tatt;Yeong, Joe;Lim, Tony Kiat Hon;Ngo, Nye-Thane;Zhang, Yongchang;Ding, Chen;Ding, Chen;Yeong, Joe;Yeong, Joe;Yeong, Joe

作者机构：

期刊名称：NATURE （ 影响因子：48.5； 五年影响因子：55.0 ）

ISSN： 0028-0836

年卷期： 2025 年 640 卷 8060 期

页码：

收录情况： SCI

摘要： Given the high recurrence rates of hepatocellular carcinoma (HCC) post-resection(1, 2-3), improved early identification of patients at high risk for post-resection recurrence would help to improve patient outcomes and prioritize healthcare resources(4, 5-6). Here we observed a spatial and HCC recurrence-associated distribution of natural killer (NK) cells in the invasive front and tumour centre from 61 patients. Using extreme gradient boosting and inverse-variance weighting, we developed the tumour immune microenvironment spatial (TIMES) score based on the spatial expression patterns of five biomarkers (SPON2, ZFP36L2, ZFP36, VIM and HLA-DRB1) to predict HCC recurrence risk. The TIMES score (hazard ratio = 88.2, P < 0.001) outperformed current standard tools for patient risk stratification including the TNM and BCLC systems. We validated the model in 231 patients from five multicentred cohorts, achieving a real-world accuracy of 82.2% and specificity of 85.7%. The predictive power of these biomarkers emerged through the integration of their spatial distributions, rather than individual marker expression levels alone. In vivo models, including NK cell-specific Spon2-knockout mice, revealed that SPON2 enhances IFN gamma secretion and NK cell infiltration at the invasive front. Our study introduces TIMES, a publicly accessible tool for predicting HCC recurrence risk, offering insights into its potential to inform treatment decisions for early-stage HCC.

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