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Spatial immune scoring system predicts hepatocellular carcinoma recurrence

Gengjie Jia, Peiqi He, Tianli Dai, Denise Goh, Jiabei Wang, Mengyuan Sun, Felicia Wee, Fuling Li, Jeffrey Chun Tatt Lim, Shuxia Hao, Yao Liu, Tony Kiat Hon Lim, Nye-Thane Ngo, Qingping Tao, Wei Wang, Ahitsham Umar, Björn Nashan, Yongchang Zhang, Chen Ding, Joe Yeong (), Lianxin Liu () and Cheng Sun ()
Additional contact information
Gengjie Jia: University of Science and Technology of China
Peiqi He: University of Science and Technology of China
Tianli Dai: University of Science and Technology of China
Denise Goh: Agency for Science Technology and Research (A*STAR)
Jiabei Wang: University of Science and Technology of China
Mengyuan Sun: University of Science and Technology of China
Felicia Wee: Agency for Science Technology and Research (A*STAR)
Fuling Li: University of Science and Technology of China
Jeffrey Chun Tatt Lim: Agency for Science Technology and Research (A*STAR)
Shuxia Hao: Chinese Academy of Agricultural Sciences
Yao Liu: University of Science and Technology of China
Tony Kiat Hon Lim: University of Science and Technology of China
Nye-Thane Ngo: Duke-NUS Medical School
Qingping Tao: University of Science and Technology of China
Wei Wang: University of Science and Technology of China
Ahitsham Umar: University of Science and Technology of China
Björn Nashan: University of Science and Technology of China
Yongchang Zhang: The Affiliated Cancer Hospital of Central South University
Chen Ding: Fudan University
Joe Yeong: Agency for Science Technology and Research (A*STAR)
Lianxin Liu: University of Science and Technology of China
Cheng Sun: University of Science and Technology of China

Nature, 2025, vol. 640, issue 8060, 1031-1041

Abstract: Abstract Given the high recurrence rates of hepatocellular carcinoma (HCC) post-resection1–3, improved early identification of patients at high risk for post-resection recurrence would help to improve patient outcomes and prioritize healthcare resources4–6. 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

Date: 2025
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DOI: 10.1038/s41586-025-08668-x

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