{
  "abstract": "Background The tumour–stroma ratio (TSR) is a potential prognostic indicator, yet hindered by quantification challenges and conflicting reports.Objective To determine whether TSR follows a non-linear prognostic pattern and to develop an artificial intelligence (AI)-powered framework for standardised TSR assessment and prognosis prediction in hepatocellular carcinoma (HCC).Design We integrated whole-slide image (WSI) data with clinical variables across a retrospective cohort (n=392) and The Cancer Genome Atlas dataset (n=168). Restricted cubic splines were used to interrogate non-linear hazard dynamics, with biological validation via transcriptomics and immunohistochemistry. An AI-driven foundation model framework was developed for TSR quantification and multimodal prognostic modelling.Results Our analysis unveiled an inverted U-shaped non-linear relationship between TSR and mortality, identifying a risk initiation threshold at 0.188 and a peak at 0.268. Transcriptomics analysis indicated that this high-risk phenotype is characterised by active tumour proliferation, stromal activation and tumour microenvironment crosstalk. Technically, AI-derived TSR showed strong correlation with expert assessment (R² >0.9). Furthermore, we developed a novel ‘Token-Guided Multimodal Fusion’ architecture to integrate WSI, TSR and clinical variables as high-dimensional tokens directly into the computational logic. Consequently, our multimodal framework demonstrated prognostic accuracy (area under the curve >0.80) compared with unimodal baselines.Conclusion This study redefines TSR assessment, shifting from manual estimation to high-dimensional semantic reasoning. By identifying the non-linear prognostic mechanics of the stroma, our token-guided framework offers a biologically interpretable solution for HCC. We suggest that the future of computational pathology may lie not in simple quantification, but in the semantic fusion of human domain knowledge with AI reasoning.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "He-Yu Huang"
    },
    {
      "affiliations": [
        "The Image Processing Center, School of Astronautics, Beihang University, Beijing, China"
      ],
      "name": "Kun Wu"
    },
    {
      "affiliations": [
        "Department of Pathology, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Li-mei Qu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Xiao-Dong Sun"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Ming-Yue Li"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Feng Wei"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Ping Zhang"
    },
    {
      "affiliations": [
        "Division of Hepatobiliary & Pancreatic Surgery, Department of Surgery, National University Hospital Singapore, Singapore"
      ],
      "name": "Alfred Wei Chieh Kow"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Yu-Guo Chen"
    },
    {
      "affiliations": [
        "Department of Pathology, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Mei-Shan Jin"
    },
    {
      "affiliations": [
        "Department of Pathology, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Liang Guo"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Wei Qiu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Meng Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Xiao-Ju Shi"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Jun-Feng Ye"
    },
    {
      "affiliations": [
        "The Image Processing Center, School of Astronautics, Beihang University, Beijing, China"
      ],
      "name": "Chuan-Hao Hu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Yue-Xuan Zhao"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Yu Huang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Zhong-Qi Fan"
    },
    {
      "affiliations": [
        "School of Engineering Medicine, Beijing Advanced Innovation Center on Biomedical Engineering, Beihang University, Beijing, China"
      ],
      "name": "Yu-Shan Zheng"
    },
    {
      "affiliations": [
        "The Image Processing Center, School of Astronautics, Beihang University, Beijing, China"
      ],
      "name": "Feng-Ying Xie"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, First Hospital of Jilin University, Changchun, Jilin, China",
        "China-Singapore Belt and Road Joint Laboratory on Liver Disease Research, First Hospital of Jilin University, Changchun, Jilin, China"
      ],
      "name": "Guo-Yue Lv"
    }
  ],
  "title": "Token-guided multimodal prognosis in hepatocellular carcinoma: a framework steered by tumour–stroma ratio",
  "uid": "4ad49192-8199-50b8-a6dd-72c71657edff"
}