Improving diagnosis and outcome prediction of gastric cancer via multimodal learning using whole slide pathological images and gene expression.

Journal: Artificial intelligence in medicine
Published Date:

Abstract

For the diagnosis and outcome prediction of gastric cancer (GC), machine learning methods based on whole slide pathological images (WSIs) have shown promising performance and reduced the cost of manual analysis. Nevertheless, accurate prediction of GC outcome may rely on multiple modalities with complementary information, particularly gene expression data. Thus, there is a need to develop multimodal learning methods to enhance prediction performance. In this paper, we collect a dataset from Ruijin Hospital and propose a multimodal learning method for GC diagnosis and outcome prediction, called GaCaMML, which is featured by a cross-modal attention mechanism and Per-Slide training scheme. Additionally, we perform feature attribution analysis via integrated gradient (IG) to identify important input features. The proposed method improves prediction accuracy over the single-modal learning method on three tasks, i.e., survival prediction (by 4.9% on C-index), pathological stage classification (by 11.6% on accuracy), and lymph node classification (by 12.0% on accuracy). Especially, the Per-Slide strategy addresses the issue of a high WSI-to-patient ratio and leads to much better results compared with the Per-Person training scheme. For the interpretable analysis, we find that although WSIs dominate the prediction for most samples, there is still a substantial portion of samples whose prediction highly relies on gene expression information. This study demonstrates the great potential of multimodal learning in GC-related prediction tasks and investigates the contribution of WSIs and gene expression, respectively, which not only shows how the model makes a decision but also provides insights into the association between macroscopic pathological phenotypes and microscopic molecular features.

Authors

  • Yuzhang Xie
    Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Qingqing Sang
    Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasm, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
  • Qian Da
    Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Guoshuai Niu
    Department of Computer Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
  • Shijie Deng
    Department of Pathology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Haoran Feng
    Department of General Surgery.
  • Yunqin Chen
    Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China; Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai, 201203, China.
  • Yuan-Yuan Li
    Basic Clinical Medicine Research Institute, China Academy of Chinese Medical Sciences, Beijing 100700, China.
  • Bingya Liu
    Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasm, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: liubingya@sjtu.edu.cn.
  • Yang Yang
    Department of Gastrointestinal Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
  • Wentao Dai
    Department of General Surgery, Shanghai Key Laboratory of Gastric Neoplasm, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Shanghai-MOST Key Laboratory of Health and Disease Genomics, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai 200237, China; Shanghai Engineering Research Center of Pharmaceutical Translation, Shanghai, 201203, China. Electronic address: wtdai@scbit.org.