Pathomics Signature for Prognosis and CA19-9 Interception in Pancreatic Ductal Adenocarcinoma: A Real-Life, Multi-Center Study.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published Date: Jan 20, 2026

Abstract

Histopathological hematoxylin and eosin (H&E) slides contain valuable prognostic information for pancreatic ductal adenocarcinoma (PDAC), yet systematic feature extraction remains challenging. This multi-center study developed and validated an automated prognostic model using deep learning on digitized whole-slide images from 873 PDAC patients with surgical resection across three academic centers. The CrossFormer architecture achieved superior performance in external validation (area under the curve [AUC] = 0.774), significantly outperforming ResNet-18 (AUC = 0.716), ResNet-50 (AUC = 0.737), and DenseNet-121 (AUC = 0.729). Gradient-weighted Class Activation Mapping identified key prognostic features including desmoplastic stroma, high nuclear-to-cytoplasmic ratio, tumor necrosis, and immune cell infiltration. The pathomics signature effectively stratified patients into low-risk and high-risk groups with significant survival differences (p < 0.001). Critically, carbohydrate antigen 19-9 (CA19-9) retained prognostic value only in low-risk patients (hazard ratio [HR] = 2.70, p < 0.001) but not in high-risk patients (HR = 0.998, p = 0.990). High-risk patients derived substantial benefit from adjuvant chemotherapy (HR = 0.56, p = 0.038), whereas low-risk patients showed no significant benefit (HR = 0.83, p = 0.562). These findings provide actionable clinical insights: treatment intensification for high-risk patients and CA19-9-guided monitoring for low-risk patients. This validated, interpretable model transforms routine H&E slides into quantitative prognostic tools, enabling personalized treatment strategies without additional testing costs.

Authors

  • Qiangda Chen
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Zhihang Xu
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Yiping Zou
    Pancreas Center, National Clinical Research Center for Cancer, State Key Laboratory of Drug ability Evaluation and Systematic Translational Medicine, Tianjin Key Laboratory of Digestive Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin's Clinical Research Center for Cancer, Tianjin, PR China.
  • Zhenlai Jiang
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Yecheng Li
    Joint International Research Laboratory of Synthetic Biology and Medicine, Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, School of Biology and Biological Engineering , South China University of Technology , Guangzhou 510006 , China.
  • Taochen He
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Hanlin Yin
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Jiali Li
    Department of Liver and Pancreatobiliary Surgery, Dongguan People's Hospital, Dongguan, Guangdong, China.
  • Yanfei An
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Jiande Han
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Yuqi Xie
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Wei Gan
    College of Computer Science, Sichuan University, Chengdu, 610064, People's Republic of China.
  • Yaolin Xu
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Wenquan Wang
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Junyi He
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Haibo Wang
    Institute of Cardiovascular Diseases, Shanghai Jiao Tong University School of Medicine, 197 Ruijin 2nd Road, Shanghai, 200025, PR China.
  • Wenchuan Wu
    Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
  • Zhenyu Ye
    Department of General Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, China.
  • Wenhui Lou
    Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
  • Jihui Hao
    Pancreas Center, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China. [email protected].
  • Liang Liu
    College of Cybersecurity, Sichuan University, Chengdu, China.
  • Jun Yu
  • Ning Pu

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