Deep Learning-Based Stratification of Gastric Cancer Patients from Hematoxylin and Eosin-Stained Whole Slide Images by Predicting Molecular Features for Immunotherapy Response.

Journal: The American journal of pathology
PMID:

Abstract

Determining the molecular characteristics of cancer patients is crucial for optimal immunotherapy decisions. The aim of this study was to screen immunotherapy beneficiaries by predicting key molecular features from hematoxylin and eosin-stained images based on deep learning models. An independent data set from Asian gastric cancer patients was included for external validation. In addition, a segmentation model (Horizontal-Vertical Network) was used to quantify the cellular composition of tumor stroma. The model performance was evaluated by measuring the area under the curve (AUC). The tumor extraction model achieved an AUC of 0.9386 and 0.9062 in the internal and external test sets, respectively. The stratification model could predict the immunotherapy-sensitive subtypes (AUC range, 0.8685 to 0.9461), the genetic mutations (AUC range, 0.8283 to 0.9225), and the pathway activity (AUC range, 0.7568 to 0.8612) fairly accurately. In external validation, the prediction performance of Epstein-Barr virus and programmed cell death ligand 1 expression status achieved AUCs of 0.7906 and 0.6384, respectively. The segmentation model identified a relatively high proportion of inflammatory cells and connective cells in some immunotherapy-sensitive subtypes. The deep learning-based models potentially may serve as a valuable tool to screen for the beneficiaries of immunotherapy in gastric cancer patients.

Authors

  • Zheng Wei
    Ministry of Education Key Laboratory of Bioinformatics, Center for Synthetic and Systems Biology, Beijing National Research Center for Information Science and Technology, Department of Automation, Tsinghua University, Beijing 100084, China.
  • Xu Zhao
    Intensive Care Unit, Hubei University of Medicine, Renmin Hospital, Shiyan, Hubei, China.
  • Jing Chen
    Department of Vascular Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China.
  • Qiuyan Sun
    Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Prevention, Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of GI Cancer Etiology and Prevention, Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
  • Zeyang Wang
    Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Prevention, Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of GI Cancer Etiology and Prevention, Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
  • Yanli Wang
    Department of Electrical Engineering and Computer Science, University of Missouri, Columbia, MO, USA.
  • Zhiyi Ye
    Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Prevention, Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of GI Cancer Etiology and Prevention, Liaoning Province, The First Hospital of China Medical University, Shenyang, China.
  • Yuan Yuan
    Department of Geriatrics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, China.
  • Liping Sun
    School of Medical Informatics Engineering, Anhui University of Chinese Medicine, Hefei, Anhui 230012, China.
  • Jingjing Jing
    Tumor Etiology and Screening Department of Cancer Institute and General Surgery, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Cancer Etiology and Prevention, Liaoning Education Department, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of GI Cancer Etiology and Prevention, Liaoning Province, The First Hospital of China Medical University, Shenyang, China. Electronic address: hellojjjing@163.com.