A multiomics analysis-assisted deep learning model identifies a macrophage-oriented module as a potential therapeutic target in colorectal cancer.

Journal: Cell reports. Medicine
PMID: 38307032

Abstract

Colorectal cancer (CRC) is a common malignancy involving multiple cellular components. The CRC tumor microenvironment (TME) has been characterized well at single-cell resolution. However, a spatial interaction map of the CRC TME is still elusive. Here, we integrate multiomics analyses and establish a spatial interaction map to improve the prognosis, prediction, and therapeutic development for CRC. We construct a CRC immune module (CCIM) that comprises FOLR2 macrophages, exhausted CD8 T cells, tolerant CD8 T cells, exhausted CD4 T cells, and regulatory T cells. Multiplex immunohistochemistry is performed to depict the CCIM. Based on this, we utilize advanced deep learning technology to establish a spatial interaction map and predict chemotherapy response. CCIM-Net is constructed, which demonstrates good predictive performance for chemotherapy response in both the training and testing cohorts. Lastly, targeting FOLR2 macrophage therapeutics is used to disrupt the immunosuppressive CCIM and enhance the chemotherapy response in vivo.

Authors

  • Xuanwen Bao
    The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Qiong Li
    Department of Burns & Wound Care Centre, 2nd Affiliated Hospital of Zhejiang University, College of Medicine, Hangzhou, 310000, Zhejiang Province, China. 2504131@zju.edu.cn.
  • Dong Chen
    School of Basic Medical Sciences, Health Science Center, Ningbo University, Ningbo, China.
  • Xiaomeng Dai
    Institute of Information Science and Electronic Engineering, Zhejiang University, Yuquan Campus, Hangzhou, Zhejiang, China.
  • Chuan Liu
    Link Sense Laboratory, Nanjing Research Institute of Electronic Technology, Nanjing, China.
  • Weihong Tian
    Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, China.
  • Hangyu Zhang
    The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
  • Yuzhi Jin
    Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China.
  • Yin Wang
    State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai 200433, China.
  • Jinlin Cheng
    State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China.
  • Chunyu Lai
    Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China.
  • Chanqi Ye
    Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China.
  • Shan Xin
    Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
  • Xin Li
    Veterinary Diagnostic Center, Shanghai Animal Disease Control Center, Shanghai, China.
  • Ge Su
  • Yongfeng Ding
    School of Intelligent Manufacturing Engineering, Chongqing University of Arts and Sciences, Chongqing, China.
  • Yangyang Xiong
    Department of Gastroenterology, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China.
  • Jindong Xie
    Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
  • Vincent Tano
    Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 637551, Republic of Singapore.
  • Yanfang Wang
    Ultrasound Medical Center, Lanzhou University Second Hospital, Lanzhou University, Lanzhou, 730030, China.
  • Wenguang Fu
    Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, People's Republic of China.
  • Shuiguang Deng
  • Weijia Fang
    Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, CN, China.
  • Jianpeng Sheng
    Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province 310003, China. Electronic address: shengjp@zju.edu.cn.
  • Jian Ruan
    Faculty of Geomatics, East China Institute of Technology, 330013, Nanchang, PR, China.
  • Peng Zhao
    Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

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