Biology-guided deep learning predicts prognosis and cancer immunotherapy response.

Journal: Nature communications
Published Date:

Abstract

Substantial progress has been made in using deep learning for cancer detection and diagnosis in medical images. Yet, there is limited success on prediction of treatment response and outcomes, which has important implications for personalized treatment strategies. A significant hurdle for clinical translation of current data-driven deep learning models is lack of interpretability, often attributable to a disconnect from the underlying pathobiology. Here, we present a biology-guided deep learning approach that enables simultaneous prediction of the tumor immune and stromal microenvironment status as well as treatment outcomes from medical images. We validate the model for predicting prognosis of gastric cancer and the benefit from adjuvant chemotherapy in a multi-center international study. Further, the model predicts response to immune checkpoint inhibitors and complements clinically approved biomarkers. Importantly, our model identifies a subset of mismatch repair-deficient tumors that are non-responsive to immunotherapy and may inform the selection of patients for combination treatments.

Authors

  • Yuming Jiang
    Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Zhicheng Zhang
  • Wei Wang
    State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078, China.
  • Weicai Huang
    Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Chuanli Chen
    Department of Medical Imaging Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Sujuan Xi
    Guangdong Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • M Usman Ahmad
    Department of Surgery, Stanford University School of Medicine, Stanford, CA, USA.
  • Yulan Ren
    Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
  • Shengtian Sang
    School of Computer Science and Technology, Dalian University of Technology, Dalian, China. sangst@mail.dlut.edu.cn.
  • Jingjing Xie
    Beijing University of Posts and Telecommunications, China.
  • Jen-Yeu Wang
    Department of Radiation Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, 94305, USA.
  • Wenjun Xiong
    Department of Gastrointestinal Surgery, Guangdong Provincial Hospital of Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
  • Tuanjie Li
    Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. gzliguoxin@163.com caishirong@yeah.net ehbhltj@hotmail.com keekee77@126.com.
  • Zhen Han
    Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.
  • Qingyu Yuan
    Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
  • Yikai Xu
  • Lei Xing
    Department of Radiation Oncology, Stanford University, CA, USA.
  • George A Poultsides
    Department of Surgery, Stanford University, Stanford, CA, USA.
  • Guoxin Li
    Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. gzliguoxin@163.com caishirong@yeah.net ehbhltj@hotmail.com keekee77@126.com.
  • Ruijiang Li
    Global Station for Quantum Medical Science and Engineering, Global Institution for Collaborative Research and Education (GI-CoRE), Proton Beam Therapy Center, North 14 West 5 Kita-ku, Sapporo, Hokkaido, 060-8648, Japan.